Results

DrugID	Drug Name	Indication	Highest status	Target Name	AD Risk Gene	MOA	Evidence Example	Distance	All Evidence
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.	-8.28	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.09	more
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.	-8.00	more
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.	-8.00	more
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.	-8.00	more
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.	-8.00	more
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.	-8.00	more
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.	-6.46	more
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.	-6.46	more
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.	-5.50	more
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.	-5.08	more
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.	-5.08	more
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.	-5.08	more
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.	-5.08	more
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.	-5.06	more
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.	-5.06	more
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.	-5.06	more
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.	-5.06	more
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.	-4.51	more
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.	-4.25	more
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.	-4.25	more
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.	-4.03	more
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.	-4.03	more
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.	-4.03	more
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.	-4.03	more
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.	-4.03	more
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.	-4.03	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.91	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.89	more
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.	-3.76	more
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.	-3.76	more
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.	-3.76	more
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.	-3.76	more
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.	-3.76	more
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.	-3.76	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.71	more
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.	-3.64	more
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.	-2.56	more
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.	-2.56	more
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.	-1.68	more
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.	-1.68	more
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.	-1.01	more
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.	-0.96	more
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.	-0.96	more
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.	-0.96	more
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.	-0.96	more
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.	-0.95	more
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.	-0.88	more
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.	-0.88	more
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.	-0.88	more
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.	-0.81	more
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.	-0.79	more
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.	-0.79	more
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.	-0.75	more
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.	-0.75	more
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.	-0.46	more
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.	-0.41	more
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.	-0.41	more
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.	-0.32	more
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.	-0.32	more
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.	0.03	more
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.	0.08	more
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.	0.08	more
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.	0.14	more
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.	0.32	more
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.	0.36	more
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.	0.56	more
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.	0.65	more

All Evidence

Target ID	AD Risk Gene	MOA	PMID	Evidence
T45593	MAPT	Inhibitor	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.
T45593	MAPT	Inhibitor	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.
T45593	MAPT	Inhibitor	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.
T45593	MAPT	Inhibitor	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.
T45593	MAPT	Inhibitor	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.
T45593	MAPT	Inhibitor	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.