Results 搜索结果
| DrugID 药品编号 |
Drug Name 药品名称 |
Indication 适应症 |
Highest status 最高状态 |
Target Name 目标名称 |
AD Risk Gene 阿尔茨海默病风险基因 |
MOA 作用机制 |
Evidence Example 证据示例 |
Distance 距离 |
All Evidence 所有证据 |
|---|---|---|---|---|---|---|---|---|---|
| D0V6OZ | CN-105 | Unclearntraumatic intracerebral hemorrhage | Phase 2 | APOE | APOE | Agonist | Here using human iPSC-derived cerebral organoid models, we find that APOE deletion increases alpha-synuclein (alphaSyn) accumulation accompanied with synaptic loss, reduction of GBA levels, lipid droplet accumulation and dysregulation of intracellular organelles. 这里利用人诱导多能干细胞衍生的脑类器官模型，我们发现APOE基因缺失会增加α-突触核蛋白（αSyn）的积累，并伴随突触丢失、GBA水平下降、脂滴积累以及细胞内细胞器的调控失常。 |
-8.28 | more 更多 |
| D03SHD | Myo-inositol | Alzheimer disease | Phase 2 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D06KWU | DWP-09031 | Alzheimer disease | Phase 1 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D07VAI | ALZ-801 | Alzheimer disease | Phase 2 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D08QDF | Systebryl | Amyloidosis | Phase 1 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D09DLP | Tramiprosate | Alzheimer disease | Phase 3 | APP | APP | Antagonist | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D0CH6B | ALZT-OP1 | Alzheimer disease | Phase 3 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D0E8HA | T-817MA | Alzheimer disease | Phase 2 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D0G7LP | Pepticlere | Alzheimer disease | Preclinical | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D0W0NU | NIC5-15 | Alzheimer disease | Phase 2 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D0X4ZL | AN-1792 | Alzheimer disease | Phase 2 | APP | APP | Inhibitor | The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-beta. 5XFAD模型过表达含有人β淀粉样前体蛋白（APP）和早老素1（PS1），其中含有五种家族性阿尔茨海默病突变，这些突变具有高APP表达量，与高淀粉样β蛋白42氨基酸物种的负担和加速积累相关。 |
-8.09 | more 更多 |
| D01EJG | RG6100 | Alzheimer disease | Phase 2 | MAPT | MAPT | Inhibitor | Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. 鉴于MAPT基因的功能获得性突变导致以tau蛋白沉积为特征的额颞叶萎缩症（FTLD），我们假设MAPT基因剂量受影响的复制也可能导致疾病。 |
-8.00 | more 更多 |
| D0I3LY | PMID28766366-Compound-Scheme22Middle | Unclear | Patented | MAPT | MAPT | Inhibitor | Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. 鉴于MAPT基因的功能获得性突变导致以tau蛋白沉积为特征的额颞叶萎缩症（FTLD），我们假设MAPT基因剂量受影响的复制也可能导致疾病。 |
-8.00 | more 更多 |
| D0I8FS | BIIB092 | Progressive supranuclear palsy | Alzheimer disease | Phase 2 | MAPT | MAPT | Inhibitor | Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. 鉴于MAPT基因的功能获得性突变导致以tau蛋白沉积为特征的额颞叶萎缩症（FTLD），我们假设MAPT基因剂量受影响的复制也可能导致疾病。 |
-8.00 | more 更多 |
| D0P8YJ | PTI-80 | Alzheimer disease | Phase 1 | MAPT | MAPT | Inhibitor | Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. 鉴于MAPT基因的功能获得性突变导致以tau蛋白沉积为特征的额颞叶萎缩症（FTLD），我们假设MAPT基因剂量受影响的复制也可能导致疾病。 |
-8.00 | more 更多 |
| D5FSV8 | TRx0237 | Alzheimer disease | Phase 3 | MAPT | MAPT | Inhibitor | Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. 鉴于MAPT基因的功能获得性突变导致以tau蛋白沉积为特征的额颞叶萎缩症（FTLD），我们假设MAPT基因剂量受影响的复制也可能导致疾病。 |
-8.00 | more 更多 |
| D05XDZ | LMT-X | Acute myeloid leukaemia | Alzheimer disease | Phase 3 | MAPT/TARDBP | TARDBP | Inhibitor | Additionally, in Drosophila models of ALS and human neuronal cells, scientists found that overexpression of TAR DNA-binding protein 43 (TDP-43) can inhibit HSPA8 transcription, leading to the dysfunction of synaptic vesicle cycling all of which is associated with microautophagy dysfunction. 此外，在肌萎缩侧索硬化症（ALS）的果蝇模型和人神经细胞中，科学家们发现TAR DNA结合蛋白43（TDP-43）的过度表达可以抑制HSPA8的转录，导致突触囊泡循环功能障碍，这一切都与微自噬功能障碍有关。 |
-6.46 | more 更多 |
| D05XDZ | LMT-X | Acute myeloid leukaemia | Alzheimer disease | Phase 3 | MAPT/TARDBP | MAPT | Inhibitor | Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. 鉴于MAPT基因的功能获得性突变导致以tau蛋白沉积为特征的额颞叶萎缩症（FTLD），我们假设MAPT基因剂量受影响的复制也可能导致疾病。 |
-6.46 | more 更多 |
| D01LOE | LY2963016 | Type-1/2 diabetes | Phase 3 | INS | INS | Agonist | Results: CNN-derived image phenotypes are significantly associated with fasting metabolites related to early lipid metabolic changes as well as insulin resistance and with genetic variants mapped to candidate genes enriched for amyloid beta degradation, tau phosphorylation, calcium ion binding-dependent synaptic loss, APP-regulated inflammation response, and insulin resistance. 结果：CNN导出的图像表型与空腹代谢物显著相关，这些代谢物与早期脂质代谢变化及胰岛素抵抗相关，并且与映射到富含β淀粉样蛋白降解、tau磷酸化、钙离子结合依赖性突触丢失、APP调控的炎症反应和胰岛素抵抗候选基因的遗传变异相关。 |
-5.50 | more 更多 |
| D01UYA | MEDI1341 | Parkinson disease | Phase 1 | SNCA | SNCA | Inhibitor | We show here, in the MPP+ (1-methyl-4-phenylpyridinium ion) cell model of parkinsonism, a time- and dose-dependent increase in the hyperphosphorylation of Tau at pSer396/404 (PHF-1-reactive Tau, p-Tau), concomitant with increased accumulation of alpha-Syn, upon treatment of cells with the neurotoxin. 在这里，我们在MPP+（1-甲基-4-苯基吡啶鎓离子）帕金森病细胞模型中显示，细胞经神经毒素处理后，Tau蛋白在pSer396/404位点的过度磷酸化（PHF-1反应性的Tau，p-Tau）随时间和剂量依赖性地增加，并伴随α-突触核蛋白（alpha-Syn）的累积增加。 |
-5.08 | more 更多 |
| D0TU9W | BIIB054 | Parkinson disease | Phase 2 | SNCA | SNCA | Inhibitor | We show here, in the MPP+ (1-methyl-4-phenylpyridinium ion) cell model of parkinsonism, a time- and dose-dependent increase in the hyperphosphorylation of Tau at pSer396/404 (PHF-1-reactive Tau, p-Tau), concomitant with increased accumulation of alpha-Syn, upon treatment of cells with the neurotoxin. 在这里，我们在MPP+（1-甲基-4-苯基吡啶鎓离子）帕金森病细胞模型中显示，细胞经神经毒素处理后，Tau蛋白在pSer396/404位点的过度磷酸化（PHF-1反应性的Tau，p-Tau）随时间和剂量依赖性地增加，并伴随α-突触核蛋白（alpha-Syn）的累积增加。 |
-5.08 | more 更多 |
| D4N2JV | PRX002 | Parkinson disease | Phase 2 | SNCA | SNCA | Inhibitor | We show here, in the MPP+ (1-methyl-4-phenylpyridinium ion) cell model of parkinsonism, a time- and dose-dependent increase in the hyperphosphorylation of Tau at pSer396/404 (PHF-1-reactive Tau, p-Tau), concomitant with increased accumulation of alpha-Syn, upon treatment of cells with the neurotoxin. 在这里，我们在MPP+（1-甲基-4-苯基吡啶鎓离子）帕金森病细胞模型中显示，细胞经神经毒素处理后，Tau蛋白在pSer396/404位点的过度磷酸化（PHF-1反应性的Tau，p-Tau）随时间和剂量依赖性地增加，并伴随α-突触核蛋白（alpha-Syn）的累积增加。 |
-5.08 | more 更多 |
| DIW37N | NPT200-11 | Multiple system atrophy | Parkinson disease | Phase 1 | SNCA | SNCA | Inhibitor | We show here, in the MPP+ (1-methyl-4-phenylpyridinium ion) cell model of parkinsonism, a time- and dose-dependent increase in the hyperphosphorylation of Tau at pSer396/404 (PHF-1-reactive Tau, p-Tau), concomitant with increased accumulation of alpha-Syn, upon treatment of cells with the neurotoxin. 在这里，我们在MPP+（1-甲基-4-苯基吡啶鎓离子）帕金森病细胞模型中显示，细胞经神经毒素处理后，Tau蛋白在pSer396/404位点的过度磷酸化（PHF-1反应性的Tau，p-Tau）随时间和剂量依赖性地增加，并伴随α-突触核蛋白（alpha-Syn）的累积增加。 |
-5.08 | more 更多 |
| D06WPM | Coprexa | Neurological disorder | Phase 3 | SOD1 | SOD1 | Inhibitor | KEY FINDINGS: The results showed that apoptosis and reactive oxygen species levels significantly increased in Abeta25-35-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. 关键发现：结果显示，在Abeta25-35处理的细胞中，凋亡和活性氧水平显著增加，而Nrf2、SOD和HO-1的mRNA和蛋白质水平下降。 |
-5.06 | more 更多 |
| D0D9NZ | Methoxyestradiol | Unclear | Phase 2 | SOD1 | SOD1 | Inhibitor | KEY FINDINGS: The results showed that apoptosis and reactive oxygen species levels significantly increased in Abeta25-35-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. 关键发现：结果显示，在Abeta25-35处理的细胞中，凋亡和活性氧水平显著增加，而Nrf2、SOD和HO-1的mRNA和蛋白质水平下降。 |
-5.06 | more 更多 |
| D0I1CQ | BIIB067 | Amyotrophic lateral sclerosis | Phase 3 | SOD1 | SOD1 | Inhibitor | KEY FINDINGS: The results showed that apoptosis and reactive oxygen species levels significantly increased in Abeta25-35-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. 关键发现：结果显示，在Abeta25-35处理的细胞中，凋亡和活性氧水平显著增加，而Nrf2、SOD和HO-1的mRNA和蛋白质水平下降。 |
-5.06 | more 更多 |
| D0T8MA | ATN-224 | Solid tumour/cancer | Phase 2 | SOD1 | SOD1 | Inhibitor | KEY FINDINGS: The results showed that apoptosis and reactive oxygen species levels significantly increased in Abeta25-35-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. 关键发现：结果显示，在Abeta25-35处理的细胞中，凋亡和活性氧水平显著增加，而Nrf2、SOD和HO-1的mRNA和蛋白质水平下降。 |
-5.06 | more 更多 |
| D09AYM | MABp1 | Colorectal cancer | Type-2 diabetes | Acne vulgaris | Atopic dermatitis | Hidradenitis suppurativa | Plaque psoriasis | Pyoderma gangreUnclearsum | Peripheral vascular disease | Phase 3 | IL1A | IL1A | Inhibitor | Subsequently, we exposed NGC0211 cells directly to AD-related factors like amyloid-beta peptides (Abeta40/42) or activated astrocyte-conditioned medium (Abeta40/42/IL-1beta/TNFalpha-treated) and evaluated biochemical stress markers, cell death indicators, cell proliferation marker (Ki67), and hmNGF release. 随后，我们将NGC0211细胞直接暴露于与阿尔茨海默病相关的因素，如β淀粉样肽（Abeta40/42）或激活的星形胶质细胞条件培养基（Abeta40/42/IL-1beta/TNFalpha处理），并评估了生物化学应激标志物、细胞死亡指标、细胞增殖标记物（Ki67）和hmNGF的释放。 |
-4.51 | more 更多 |
| D0I9XH | Celastrol | Motor neurone disease | Preclinical | TNF/IL1B | TNF | Suppressor | Subsequently, we exposed NGC0211 cells directly to AD-related factors like amyloid-beta peptides (Abeta40/42) or activated astrocyte-conditioned medium (Abeta40/42/IL-1beta/TNFalpha-treated) and evaluated biochemical stress markers, cell death indicators, cell proliferation marker (Ki67), and hmNGF release. 随后，我们将NGC0211细胞直接暴露于与阿尔茨海默病相关的因素，如β淀粉样肽（Abeta40/42）或激活的星形胶质细胞条件培养基（Abeta40/42/IL-1beta/TNFalpha处理），并评估了生物化学应激标志物、细胞死亡指标、细胞增殖标记物（Ki67）和hmNGF的释放。 |
-4.25 | more 更多 |
| D0I9XH | Celastrol | Motor neurone disease | Preclinical | TNF/IL1B | IL1B | Suppressor | In oxidatively-stressed neural cells and rodents' brains, cytosolic oxidatively-damaged mitochondrial DNA accumulated and increased antiviral and inflammatory proteins, including cleaved caspase-1, interleukin-1beta, and interferon-beta. 在氧化应激的神经细胞和啮齿动物的大脑中，胞质氧化损伤的线粒体DNA累积增加，并伴有抗病毒和炎症蛋白的增加，包括裂解的胱天蛋白酶-1、白细胞介素-1β和干扰素-β。 |
-4.25 | more 更多 |
| D0F7DS | PMID26161698-Compound-18 | Unclear | Patented | GSK3B/CDK5 | GSK3B | Inhibitor | We further showed that miR-219-5p could mediate a decrease in the protein levels of tau-tubulin kinase 1 (TTBK1) and glycogen synthase kinase 3beta (GSK-3beta) by directly binding to their 3'-untranslated region, thereby promoting the phosphorylation of tau in SH-SY5Y Cells. 我们进一步表明，miR-219-5p可通过直接结合tau-微管蛋白激酶1（TTBK1）和糖原合成酶激酶3β（GSK-3β）的3'非翻译区来介导这些蛋白水平的降低，从而促进SH-SY5Y细胞中tau蛋白的磷酸化。 |
-4.03 | more 更多 |
| D0F7DS | PMID26161698-Compound-18 | Unclear | Patented | GSK3B/CDK5 | CDK5 | Inhibitor | Inhibition of miR-132 in primary human neurons and neural cells leads to increased NOS1 levels and triggers excessive production of nitric oxide, followed by aberrant S-nitrosylation (SNO) of specific proteins associated with neurodegeneration and tau pathology, such as cyclin-dependent kinase 5, dynamin-related protein 1, and glyceraldehyde-3-phosphate dehydrogenase. 在人原代神经元和神经细胞中抑制miR-132会导致NOS1水平升高并触发一氧化氮的过度产生，随后出现特定蛋白质异常的S-亚硝基化（SNO），这些蛋白质与神经退行性疾病和tau病理相关，如周期依赖性激酶5、动力蛋白相关蛋白1和甘油醛-3-磷酸脱氢酶。 |
-4.03 | more 更多 |
| D00EHX | TT-301 | Alzheimer disease | Phase 1 | IL1B | IL1B | Inhibitor | In oxidatively-stressed neural cells and rodents' brains, cytosolic oxidatively-damaged mitochondrial DNA accumulated and increased antiviral and inflammatory proteins, including cleaved caspase-1, interleukin-1beta, and interferon-beta. 在氧化应激的神经细胞和啮齿动物的大脑中，胞质氧化损伤的线粒体DNA累积增加，并伴有抗病毒和炎症蛋白的增加，包括裂解的胱天蛋白酶-1、白细胞介素-1β和干扰素-β。 |
-4.03 | more 更多 |
| D07NSU | Glucosamine | Osteoarthritis | Approved | IL1B | IL1B | Inhibitor | In oxidatively-stressed neural cells and rodents' brains, cytosolic oxidatively-damaged mitochondrial DNA accumulated and increased antiviral and inflammatory proteins, including cleaved caspase-1, interleukin-1beta, and interferon-beta. 在氧化应激的神经细胞和啮齿动物的大脑中，胞质氧化损伤的线粒体DNA累积增加，并伴有抗病毒和炎症蛋白的增加，包括裂解的胱天蛋白酶-1、白细胞介素-1β和干扰素-β。 |
-4.03 | more 更多 |
| D0N1FS | Diacerein | Unclear | Phase 4 | IL1B | IL1B | Inhibitor | In oxidatively-stressed neural cells and rodents' brains, cytosolic oxidatively-damaged mitochondrial DNA accumulated and increased antiviral and inflammatory proteins, including cleaved caspase-1, interleukin-1beta, and interferon-beta. 在氧化应激的神经细胞和啮齿动物的大脑中，胞质氧化损伤的线粒体DNA累积增加，并伴有抗病毒和炎症蛋白的增加，包括裂解的胱天蛋白酶-1、白细胞介素-1β和干扰素-β。 |
-4.03 | more 更多 |
| D0R4ZT | Gallium nitrate | Hypercalcaemia | Approved | IL1B | IL1B | Inhibitor | In oxidatively-stressed neural cells and rodents' brains, cytosolic oxidatively-damaged mitochondrial DNA accumulated and increased antiviral and inflammatory proteins, including cleaved caspase-1, interleukin-1beta, and interferon-beta. 在氧化应激的神经细胞和啮齿动物的大脑中，胞质氧化损伤的线粒体DNA累积增加，并伴有抗病毒和炎症蛋白的增加，包括裂解的胱天蛋白酶-1、白细胞介素-1β和干扰素-β。 |
-4.03 | more 更多 |
| D03DPZ | INK128 | Breast cancer | Multiple myeloma | Phase 2 | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D03FCF | Novolimus | Artery steUnclearsis | Approved | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D03LJR | Sirolimus | Organ transplant rejection | Multiple myeloma | Dutch elm disease | Approved | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D08PSC | BI 860585 | Solid tumour/cancer | Phase 1 | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D0ES1Q | Temsirolimus | Renal cell carciUnclearma | Approved | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D0H7XL | OSI-027 | Renal cell carciUnclearma | Phase 2 | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D0K3QS | Everolimus | Renal cell carciUnclearma | Kidney cancer | Approved | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D0O3CV | Ridaforolimus | Sarcoma | Phase 3 | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D0QN5M | LAM-001 | Lymphangioleiomyomatosis | Phase 1 | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D0U8QH | GDC-0349 | Unclearn-hodgkin lymphoma | Phase 1 | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D0W3UV | ABI-009 | Solid tumour/cancer | Malignant perivascular epithelioid cell tumour | Unclearn-muscle invasive bladder cancer | Pulmonary arterial hypertension | Phase 2 | MTOR | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-3.91 | more 更多 |
| D00ZFP | Estrone | MeUnclearpausal and postmeUnclearpausal disorder | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D06NXY | Ethinyl Estradiol | Female hypogonadism | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D08QMX | Estradiol | Breast cancer | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D09ZQN | Dienestrol | Atrophic vaginitis | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D0J1ML | Mestranol | Contraception | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D0N6YV | Cenestin | MeUnclearpause symptom | Osteoporosis | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D0NZ3C | TTC-352 | Breast cancer | Phase 1 | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D0Y2NE | Diethylstilbestrol | GoUnclearrrheal vaginitis | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D0Z1FX | Estriol | Hormone deficiency | Multiple sclerosis | Approved | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| DT4WU3 | TTC-352 | Metastatic melaUnclearma | Phase 1 | ESR1 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失被认为更有可能导致与阿尔茨海默病相关的记忆损害和淀粉样蛋白生成。 |
-3.89 | more 更多 |
| D02QWY | BMS-754807 | Unclear | Phase 1 | AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变极大地影响了TREM2的吞噬作用及其拮抗NFκB激活的能力，并显著阻止了野生型TREM2观察到的PI3K/AKT通路的激活。 |
-3.76 | more 更多 |
| D07SYZ | RX-0201 | Solid tumour/cancer | Renal cell carciUnclearma | Pancreatic cancer | Phase 2 | AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变极大地影响了TREM2的吞噬作用及其拮抗NFκB激活的能力，并显著阻止了野生型TREM2观察到的PI3K/AKT通路的激活。 |
-3.76 | more 更多 |
| D09CCZ | Triciribine prodrug | Solid tumour/cancer | Phase 1/2 | AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变极大地影响了TREM2的吞噬作用及其拮抗NFκB激活的能力，并显著阻止了野生型TREM2观察到的PI3K/AKT通路的激活。 |
-3.76 | more 更多 |
| D0I4TH | GDC-0068 | Breast cancer | Colorectal cancer | Prostate cancer | Gastric adeUnclearcarciUnclearma | Solid tumour/cancer | Phase 3 | AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变极大地影响了TREM2的吞噬作用及其拮抗NFκB激活的能力，并显著阻止了野生型TREM2观察到的PI3K/AKT通路的激活。 |
-3.76 | more 更多 |
| D0L8PZ | ARQ 751 | Solid tumour/cancer | Phase 1 | AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变极大地影响了TREM2的吞噬作用及其拮抗NFκB激活的能力，并显著阻止了野生型TREM2观察到的PI3K/AKT通路的激活。 |
-3.76 | more 更多 |
| D0X7CV | PTX-200 | Parkinson disease | Breast cancer | Acute myeloid leukaemia | Ovarian cancer | Phase 2 | AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变极大地影响了TREM2的吞噬作用及其拮抗NFκB激活的能力，并显著阻止了野生型TREM2观察到的PI3K/AKT通路的激活。 |
-3.76 | more 更多 |
| D00FKF | Pyrrolo-pyridine derivative 2 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D00GWE | Bidentate ligands of Markush derivative 2 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D01EIT | Pyrrolo-pyrimidine derivative 8 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D01PFZ | Pyridopyrimidinone derivative 2 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D01YHY | PMID28117607-Compound-20 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D02YTB | Pyrrolo-pyrimidine derivative 9 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D03GDC | Pyrrolo-pyridine derivative 1 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D03HNU | Hydrazide derivative 5 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D03YBQ | DNL151 | Parkinson disease | Phase 1 | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D04WND | Pyridopyrimidinone derivative 1 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D06FIH | Azaindazole derivative 1 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D07FFA | PMID28117607-Compound-7 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D07SEG | Oxindole derivative 2 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D08VBG | PMID28117607-Compound-5 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D08WVK | Oxindole derivative 3 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0C5HR | Pyrrolo-pyrimidine derivative 10 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0D6DN | Aminopyridine derivative 3 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0DP6U | Azaindazole derivative 3 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0FS9X | Fused thiophene derivative 1 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0GJ4G | Pyrrolo-pyrimidine derivative 1 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0HY0H | Hydrazide derivative 4 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0K6UV | DNL201 | Parkinson disease | Phase 1 | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0M5BR | PMID28117607-Compound-21 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0NO4O | Azaindazole derivative 2 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0O8AP | PMID28117607-Compound-4 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0PY1G | Hydrazide derivative 3 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0Q6VL | Pyrrolo-pyridazine derivative 1 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0QK7K | Oxindole derivative 4 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0S4IB | Pyridopyrimidinone derivative 3 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0SV0D | Bidentate ligands of Markush derivative 1 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0V8XG | PMID28117607-Compound-6 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0X8LX | Aminopyridine derivative 2 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0XY1J | Pyrrolo-pyrimidine derivative 11 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D0ZW5B | Azaindazole derivative 4 | Unclear | Patented | LRRK2 | LRRK2 | Inhibitor | Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. LRRK2（富含亮氨酸重复序列激酶2）中的杂合性激酶功能获得性变异导致所有帕金森病（PD）病例的1-2%，尽管这种表现是不完全的并且与年龄相关。 |
-3.71 | more 更多 |
| D02SYV | Lenzilumab | Coronavirus Disease 2019 (COVID-19) | Chronic myelogeUnclearus leukaemia | Phase 2 | CSF2 | CSF2 | Antagonist | Importantly, compound 12 also exhibits highly efficacious cellular activity, and is capable of attenuating growth factor stimulated ERK1/2 activation and proliferation in HEK293 cells as well as blocking SHP2 gain-of-function mutant-induced hematopoietic progenitor hyperproliferation in response to GM-CSF at compound concentrations of 5-10 muM. 重要的是，化合物12也表现出高效的细胞活性，能够抑制生长因子刺激下的HEK293细胞中ERK1/2的激活和增殖，以及在5-10 μM浓度下阻断SHP2功能获得性突变引起的造血祖细胞对GM-CSF的超增殖。 |
-3.64 | more 更多 |
| D08OOJ | CB-5083 | Multiple myeloma | Solid tumour/cancer | Phase 1 | VCP | VCP | Inhibitor | Mutation at codon 155, a known mutational hotspot in VCP protein is an important factor that could impair ATPase activity of the D1-domain by affecting D1-D2 linker, the linker is capable of inducing asymmetry in subunit association into a VCP hexamer. 第155密码子处的突变，是VCP蛋白中已知的突变热点，是一个重要因素，它可能通过影响D1-D2连接区来损害D1结构域的ATP酶活性；该连接区能够诱导VCP六聚体亚单位结合的不对称性。 |
-2.56 | more 更多 |
| DFC0V4 | CB-5339 | Acute myeloid leukaemia | Myelodysplastic syndrome | Phase 1 | VCP | VCP | Inhibitor | Mutation at codon 155, a known mutational hotspot in VCP protein is an important factor that could impair ATPase activity of the D1-domain by affecting D1-D2 linker, the linker is capable of inducing asymmetry in subunit association into a VCP hexamer. 第155密码子处的突变，是VCP蛋白中已知的突变热点，是一个重要因素，它可能通过影响D1-D2连接区来损害D1结构域的ATP酶活性；该连接区能够诱导VCP六聚体亚单位结合的不对称性。 |
-2.56 | more 更多 |
| D05FGR | R-flurbiprofen | Unclear | Phase 2 | PSEN1/PSEN2/APH1A/APH1B/NCSTN/PSENEN | PSEN1 | Inhibitor | Our data demonstrated that human Val97Leu mutant presenilin-1 causes spatial memory deficit in mice and increases tau phosphorylation level in glycogen synthase kinase-3-dependent manner. 我们的数据显示，人类Val97Leu突变型早老蛋白1导致小鼠的空间记忆缺陷，并以糖原合成酶激酶-3依赖的方式增加tau蛋白磷酸化水平。 |
-1.68 | more 更多 |
| D05FGR | R-flurbiprofen | Unclear | Phase 2 | PSEN1/PSEN2/APH1A/APH1B/NCSTN/PSENEN | PSEN2 | Inhibitor | By generating novel tools for measuring Ca2+ in living cells, and combining different approaches, we showed that FAD-linked PS2 mutants significantly alter cell Ca2+ signaling and brain network activity, as summarized below. 通过开发测量活细胞中Ca2+的新工具，并结合不同方法，我们证明了FAD相关PS2突变体显著改变了细胞Ca2+信号传导和大脑网络活动，总结如下。 |
-1.68 | more 更多 |
| D0WP2R | AC-201 | Type-2 diabetes | Phase 2 | IL1B/CASP1 | IL1B | Inhibitor | In oxidatively-stressed neural cells and rodents' brains, cytosolic oxidatively-damaged mitochondrial DNA accumulated and increased antiviral and inflammatory proteins, including cleaved caspase-1, interleukin-1beta, and interferon-beta. 在氧化应激的神经细胞和啮齿动物的大脑中，胞质氧化损伤的线粒体DNA累积增加，并伴有抗病毒和炎症蛋白的增加，包括裂解的胱天蛋白酶-1、白细胞介素-1β和干扰素-β。 |
-1.01 | more 更多 |
| D01PGR | SAR245409 | Solid tumour/cancer | Phase 2 | MTOR/PIK3CG | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-0.96 | more 更多 |
| D03IXK | ME-344 | Breast cancer | Solid tumour/cancer | Phase 1/2 | MTOR/MAPKAP1 | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-0.96 | more 更多 |
| D03NJY | SF1126 | Head and neck cancer | Solid tumour/cancer | Hepatocellular carciUnclearma | Phase 2 | MTOR/PIK3CG | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-0.96 | more 更多 |
| D0Z2UQ | AZD2014 | Solid tumour/cancer | Phase 2 | MTOR/MAPKAP1 | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-0.96 | more 更多 |
| D0M8PD | Estrogen | MeUnclearpause symptom | Approved | ESR1/ESR2 | ESR1 | Agonist | The loss of ERalpha expression has been noted to more likely contribute to AD-related memory impairment and amyloidogenesis. ERα表达的缺失更有可能导致阿尔茨海默病相关的记忆损伤和淀粉样蛋白生成。 |
-0.95 | more 更多 |
| D01ZAQ | AZD5363 | Triple negative breast cancer | Solid tumour/cancer | Phase 3 | AKT1/AKT3 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变严重影响TREM2的吞噬作用及其拮抗NFκB激活的能力，并且值得注意的是，这些突变阻止了野生型TREM2观察到的PI3K/AKT途径的激活。 |
-0.88 | more 更多 |
| D07DWF | ARQ 092 | Proteus syndrome | Solid tumour/cancer | Phase 2 | AKT1/AKT3 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变严重影响TREM2的吞噬作用及其拮抗NFκB激活的能力，并且值得注意的是，这些突变阻止了野生型TREM2观察到的PI3K/AKT途径的激活。 |
-0.88 | more 更多 |
| D07QBF | PMID28460551-Compound-6 | Unclear | Patented | SRC/AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变严重影响TREM2的吞噬作用及其拮抗NFκB激活的能力，并且值得注意的是，这些突变阻止了野生型TREM2观察到的PI3K/AKT途径的激活。 |
-0.88 | more 更多 |
| D00GPQ | PF-03084014 | Desmoid tumour | Alzheimer disease | Solid tumour/cancer | Phase 3 | APP/APH1A/APH1B/NCSTN/PSENEN/PSEN1 | APP | Inhibitor | In mammalian cells, siRNA-mediated knock-down of PE synthesis resulted in decreased Abeta owing to a dual effect: promoted alpha-secretase cleavage and decreased gamma-secretase processing of APP. 在哺乳动物细胞中，siRNA介导的PE合成敲低导致Abeta减少，这是由于双重效应：促进α-分泌酶切割并减少γ-分泌酶对APP的处理。 |
-0.81 | more 更多 |
| D01KTG | HDM201 | Haematological malignancy | Liposarcoma | Solid tumour/cancer | Phase 1 | MDM2/TP53 | TP53 | Inhibitor | Finally, PS1 mutations enhance p53 activity in human embryonic kidney 293 cells and p53 expression in FAD-affected brains. 最后，PS1突变增强了人胚肾293细胞中的p53活性和FAD受影响大脑中的p53表达。 |
-0.79 | more 更多 |
| D04SXL | APG-115 | Prolymphocytic leukaemia | Solid tumour/cancer | Phase 2 | MDM2/TP53 | TP53 | Inhibitor | Finally, PS1 mutations enhance p53 activity in human embryonic kidney 293 cells and p53 expression in FAD-affected brains. 最后，PS1突变增强了人胚肾293细胞中的p53活性和FAD受影响大脑中的p53表达。 |
-0.79 | more 更多 |
| D0G2IC | (S)-FLURBIPROFEN | Myalgia | Scapulohumeral periarthritis | Osteoarthritis | Preregistration | PTGS1/PTGS2/PSEN1/PSEN2/APH1A/APH1B/NCSTN/PSENEN | PSEN1 | Inhibitor | Our data demonstrated that human Val97Leu mutant presenilin-1 causes spatial memory deficit in mice and increases tau phosphorylation level in glycogen synthase kinase-3-dependent manner. 我们的数据显示，人类Val97Leu突变型早老蛋白1导致小鼠的空间记忆缺陷，并以糖原合成酶激酶-3依赖的方式增加tau蛋白磷酸化水平。 |
-0.75 | more 更多 |
| D0G2IC | (S)-FLURBIPROFEN | Myalgia | Scapulohumeral periarthritis | Osteoarthritis | Preregistration | PTGS1/PTGS2/PSEN1/PSEN2/APH1A/APH3B/NCSTN/PSENEN | PSEN2 | Inhibitor | By generating novel tools for measuring Ca2+ in living cells, and combining different approaches, we showed that FAD-linked PS2 mutants significantly alter cell Ca2+ signaling and brain network activity, as summarized below. 通过开发测量活细胞中Ca2+的新工具，并结合不同方法，我们证明了FAD相关PS2突变体显著改变了细胞Ca2+信号传导和大脑网络活动，总结如下。 |
-0.75 | more 更多 |
| D0S5LO | PF-04449913 | Chronic myelomoUnclearcytic leukaemia | Solid tumour/cancer | Approved | MTOR/SMO | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
-0.46 | more 更多 |
| D00PWQ | KENPAULLONE | Unclear | Patented | GSK3A/GSK3B/CDK1/CDK5/CCNB1 | GSK3B | Inhibitor | We further showed that miR-219-5p could mediate a decrease in the protein levels of tau-tubulin kinase 1 (TTBK1) and glycogen synthase kinase 3beta (GSK-3beta) by directly binding to their 3'-untranslated region, thereby promoting the phosphorylation of tau in SH-SY5Y Cells. 我们进一步表明miR-219-5p可以通过直接结合至tau-微管蛋白激酶1 (TTBK1) 和糖原合成酶激酶3β (GSK-3β) 的3'非翻译区来介导这两种蛋白质水平的降低，从而促进SH-SY5Y细胞中tau蛋白的磷酸化。 |
-0.41 | more 更多 |
| D00PWQ | KENPAULLONE | Unclear | Patented | GSK3A/GSK3B/CDK1/CDK5/CCNB1 | CDK5 | Inhibitor | Inhibition of miR-132 in primary human neurons and neural cells leads to increased NOS1 levels and triggers excessive production of nitric oxide, followed by aberrant S-nitrosylation (SNO) of specific proteins associated with neurodegeneration and tau pathology, such as cyclin-dependent kinase 5, dynamin-related protein 1, and glyceraldehyde-3-phosphate dehydrogenase. 在人原代神经元和神经细胞中抑制miR-132会导致NOS1水平升高，并触发一氧化氮的过度产生，随后是特定蛋白质的异常S-亚硝基化 (SNO)，这些蛋白质与神经退行性疾病和tau病理有关，如周期素依赖性激酶5、动力相关蛋白1和甘油醛-3-磷酸脱氢酶。 |
-0.41 | more 更多 |
| D06KCF | Mavrilimumab | Rheumatoid arthritis | Phase 2 | CSF2/CSF2RA | CSF2 | Antagonist | Importantly, compound 12 also exhibits highly efficacious cellular activity, and is capable of attenuating growth factor stimulated ERK1/2 activation and proliferation in HEK293 cells as well as blocking SHP2 gain-of-function mutant-induced hematopoietic progenitor hyperproliferation in response to GM-CSF at compound concentrations of 5-10 muM. 重要的是，化合物12也表现出高效的细胞活性，能够抑制生长因子刺激下的HEK293细胞中ERK1/2的激活和增殖，以及在5-10 μM浓度下阻断SHP2功能获得性突变引起的造血祖细胞对GM-CSF的超增殖。 |
-0.32 | more 更多 |
| D0YO4B | Cabiralizumab | Solid tumour/cancer | Pancreatic cancer | Phase 2 | CSF2/CSF1R | CSF2 | Antagonist | Importantly, compound 12 also exhibits highly efficacious cellular activity, and is capable of attenuating growth factor stimulated ERK1/2 activation and proliferation in HEK293 cells as well as blocking SHP2 gain-of-function mutant-induced hematopoietic progenitor hyperproliferation in response to GM-CSF at compound concentrations of 5-10 muM. 重要的是，化合物12也表现出高效的细胞活性，能够抑制生长因子刺激下的HEK293细胞中ERK1/2的激活和增殖，以及在5-10 μM浓度下阻断SHP2功能获得性突变引起的造血祖细胞对GM-CSF的超增殖。 |
-0.32 | more 更多 |
| D0TU7B | PQR309 | Squamous head and neck cell carciUnclearm | Pain | Phase 2 | MTOR/PIK3CG/PIK3CB | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
0.03 | more 更多 |
| D06HYF | M2698 | Solid tumour/cancer | Phase 1 | AKT1/RPS6KB1/AKT3 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变严重影响TREM2的吞噬作用及其拮抗NFκB激活的能力，并且值得注意的是，这些突变阻止了野生型TREM2观察到的PI3K/AKT途径的激活。 |
0.08 | more 更多 |
| D0I6VU | Enzastaurin | Unclearn-hodgkin lymphoma | Diffuse large B-cell lymphoma | Glioblastoma multiforme | Central nervous system disease | Phase 3 | PIK3CG/AKT1/PRKCB | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变严重影响TREM2的吞噬作用及其拮抗NFκB激活的能力，并且值得注意的是，这些突变阻止了野生型TREM2观察到的PI3K/AKT途径的激活。 |
0.08 | more 更多 |
| DY4OZ6 | Thymoquinone | Polycystic ovarian syndrome | Phase 2/3 | BCL2/BAX/TP53 | TP53 | Inhibitor | Finally, PS1 mutations enhance p53 activity in human embryonic kidney 293 cells and p53 expression in FAD-affected brains. 最后，PS1突变增强了人胚肾293细胞中的p53活性和FAD受影响大脑中的p53表达。 |
0.14 | more 更多 |
| D06TZZ | CAT 1004 | Duchenne dystrophy | Type-2 diabetes | Phase 2 | NFKB1/NFKB2/RELA/RELB/REL/NFKB1 | NFKB1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变严重影响TREM2的吞噬作用及其拮抗NFκB激活的能力，并且值得注意的是，这些突变阻止了野生型TREM2观察到的PI3K/AKT途径的激活。 |
0.32 | more 更多 |
| D00BUO | MM-141 | Solid tumour/cancer | Pancreatic cancer | Phase 2 | MTOR/IGF1R/ERBB3 | MTOR | Inhibitor | Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. 具体而言，我们发现自噬抑制增加了TDP-43 C末端片段的积累，而mTOR（一种参与自噬调控的关键蛋白激酶）的抑制减少了25 kDa C末端片段的积累，并恢复了TDP-43的定位。 |
0.36 | more 更多 |
| D0YB3W | CI-1033 | Lymphoma | Phase 2 | EGFR/ERBB2/ERBB4/AKT1 | AKT1 | Inhibitor | TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFkappaB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. TREM2突变严重影响TREM2的吞噬作用及其拮抗NFκB激活的能力，并且值得注意的是，这些突变阻止了野生型TREM2观察到的PI3K/AKT途径的激活。 |
0.56 | more 更多 |
| DT3OE6 | AL102 | Desmoid tumour | Phase 2 | APH1A/APH1B/NCSTN/PSENEN/PSEN1 | PSEN1 | Inhibitor | Our data demonstrated that human Val97Leu mutant presenilin-1 causes spatial memory deficit in mice and increases tau phosphorylation level in glycogen synthase kinase-3-dependent manner. 我们的数据显示，人类Val97Leu突变型早老蛋白1导致小鼠的空间记忆缺陷，并以糖原合成酶激酶-3依赖的方式增加tau蛋白磷酸化水平。 |
0.65 | more 更多 |
All Evidence
所有证据
| Target ID 药品编号 |
AD Risk Gene 阿尔茨海默病风险基因 |
MOA 作用机制 |
PMID PubMed编号 |
Evidence 证据 |
|---|---|---|---|---|
| T45593 | MAPT 微管相关蛋白 tau |
Inhibitor 抑制剂 |
17707586 | Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. 由于MAPT基因的增益型突变会导致以tau蛋白沉积为特征的额颞叶变性疾病（FTLD），我们假设影响基因剂量的MAPT基因复制也可能引起疾病。 |
| T45593 | MAPT 微管相关蛋白 tau |
Inhibitor 抑制剂 |
36915196 | The association between mutations in the MAPT gene and development of fronto-temporal dementia with Parkinsonism-linked to chromosome 17 (FTLD-17) has paved the way for dysfunctional Tau, being considered sufficient for causing neurodegeneration and dementia even in absence of amyloid pathology. MAPT基因突变与额颞叶变性疾病（FTLD）和帕金森病相关联的染色体17型（FTLD-17）的发展之间的关联，为功能失调的tau蛋白的研究铺平了道路，即使在没有淀粉样蛋白病理的情况下，也被认为是足以引起神经退行性和痴呆的。 |
| T45593 | MAPT 微管相关蛋白 tau |
Inhibitor 抑制剂 |
36927491 | To the contrary, in participants carrying mutations in the MAPT gene that are known to cause tauopathies other than AD, blood-based p-tau181 levels remained normal as in healthy controls, and in the case of specific mutations the concentrations appeared to be further decreased compared with normal controls. 相反，在携带已知会导致除阿尔茨海默病（AD）之外的其他tau蛋白病的MAPT基因突变的参与者中，血液p-tau181水平保持正常，与健康对照组一样，并且在特定突变的情况下，其浓度似乎与正常对照组相比进一步降低。 |
| T45593 | MAPT 微管相关蛋白 tau |
Inhibitor 抑制剂 |
36906636 | These findings imply that haplotype- and disease-specific expression and splicing of MAPT may contribute to the association of H1-homozygosity with sporadic PD. 这些发现表明，MAPT的单倍型和疾病特异性表达及剪接可能有助于H1型纯合性与散发性帕金森病（PD）之间的关联。 |
| T45593 | MAPT 微管相关蛋白 tau |
Inhibitor 抑制剂 |
36906636 | Taken together, our results show that the MAPT haplotype influences overall MAPT expression and the PD status leads to increased insoluble tau protein in parallel with insoluble alpha-syn aggregates. 综合来看，我们的结果表明MAPT单倍型影响MAPT的整体表达，并且帕金森病（PD）状态导致不溶性tau蛋白的增加与不溶性α-突触核蛋白聚集体的增加是并行的。 |
| T45593 | MAPT 微管相关蛋白 tau |
Inhibitor 抑制剂 |
36744338 | However, it is important to remember that the p.P301 L MAPT mutation used to create AD models is known to cause non-AD tauopathies in humans (e.g., progressive supranuclear palsy, globular glial tauopathy) which instead typically present with frontotemporal dementia clinically. 然而，重要的是要记住，用于创建阿尔茨海默病（AD）模型的p.P301L MAPT突变已知在人类中会引起非AD型的tau蛋白病（例如，进行性核上性麻痹，球状胶质细胞tau蛋白病），这些病在临床上通常表现为额颞叶痴呆。 |