Verubecestat

Summary

Verubecestat (CHEMBL3301601) is a phase-3 clinical-stage small molecule targeting BACE1 and BACE2; indicated across 1 condition including alzheimer disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (BACE1, BACE2)
• Indications: 1 condition
• Clinical trials: 3
• Chemistry: 409.4 Da · C17H17F2N5O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3301601
Name	Verubecestat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	51352361
Molecular formula	C17H17F2N5O3S
Molecular weight	409.4
InChIKey	YHYKUSGACIYRML-KRWDZBQOSA-N

SMILES: C[C@]1(CS(=O)(=O)N(C(=N1)N)C)C2=C(C=CC(=C2)NC(=O)C3=NC=C(C=C3)F)F

IUPAC name: N-[3-[(5R)-3-amino-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-5-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide

Also known as: MK-8931, SCH 900931, SCH-900931, SCH900931, Verubecestat, VERUBECESTAT, VERUBECESTAT (MK-8931)

Patent coverage: 249 distinct patent families (590 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 523 (89%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
BACE1	beta-secretase 1	Competitive	9.47	0.1%	P56817
BACE2	beta-secretase 2	Inhibition	9.43	0%	Q9Y5Z0

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Voltage-gated inwardly rectifying potassium channel KCNH2, Beta-secretase 2, Beta-secretase 1.

Bioactivity

ChEMBL activities: 25 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BACE2	9.43	Ki	0.37	nM	CHEMBL_ACT_16277833
BACE2	9.43	Ki	0.37	nM	CHEMBL_ACT_17661789
BACE2	9.43	Ki	0.37	nM	CHEMBL_ACT_26590112
BACE2	9.43	Ki	0.37	nM	CHEMBL_ACT_26595788
BACE2	9.42	IC50	0.38	nM	CHEMBL_ACT_18473795
BACE1	9.4	IC50	0.4	nM	CHEMBL_ACT_18515062
BACE1	9.4	Ki	0.4	nM	CHEMBL_ACT_24349493
BACE2	9.33	Ki	0.47	nM	CHEMBL_ACT_16322769
BACE2	9.33	Ki	0.47	nM	CHEMBL_ACT_16346923
BACE2	9.33	Ki	0.47	nM	CHEMBL_ACT_26576032
BACE2	9.33	Ki	0.47	nM	CHEMBL_ACT_26595800
BACE1	8.76	Ki	1.75	nM	CHEMBL_ACT_17661778
BACE1	8.76	Ki	1.75	nM	CHEMBL_ACT_17681400
BACE1	8.72	IC50	1.9	nM	CHEMBL_ACT_23203103
BACE2	8.72	IC50	1.9	nM	CHEMBL_ACT_23203109
BACE1	8.7	Ki	2	nM	CHEMBL_ACT_24794083
BACE1	8.66	IC50	2.2	nM	CHEMBL_ACT_18473790
BACE1	8.66	Ki	2.2	nM	CHEMBL_ACT_24661387
BACE1	8.4	IC50	4	nM	CHEMBL_ACT_24794098
BACE1	8.31	Ki	4.88	nM	CHEMBL_ACT_16337468
BACE1	8.31	Ki	4.88	nM	CHEMBL_ACT_17681404
BACE2	7.96	Ki	10.9	nM	CHEMBL_ACT_24349497
BACE1	7.68	IC50	20.7	nM	CHEMBL_ACT_18989307
BACE1	7.07	IC50	85	nM	CHEMBL_ACT_23162340
KCNH2	5.66	IC50	2200	nM	CHEMBL_ACT_24794169

Target pathways

Aggregated over 2 target gene(s): BACE1, BACE2.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Metabolism of proteins	1	BACE1
Amyloid fiber formation	1	BACE1

Dominant GO biological processes

GO term	Targets
proteolysis	2
membrane protein ectodomain proteolysis	2
protein processing	2
amyloid-beta metabolic process	2
response to lead ion	1
amyloid-beta formation	1
swimming behavior	1
amyloid precursor protein catabolic process	1
positive regulation of neuron apoptotic process	1
detection of mechanical stimulus involved in sensory perception of pain	1
prepulse inhibition	1
cellular response to copper ion	1
cellular response to manganese ion	1
presynaptic modulation of chemical synaptic transmission	1
signaling receptor ligand precursor processing	1

Indications & clinical

Indications

1 indication (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
Alzheimer disease	2	MONDO:0004975	MONDO:0004975

Clinical trials

Total trials: 3.

Phase distribution

Phase	Trials
PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01496170	PHASE1	COMPLETED	A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer’s Disease (MK-8931-010 AM1 [P07820 AM1])
NCT01537757	PHASE1	COMPLETED	A Two-Part, Single-Dose Study of the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (MK-8931-009 [P08535])
NCT02910739	PHASE1	COMPLETED	An Open-Label Study Investigating MK-8931 in Participants With Mild and Moderate Hepatic Insufficiency (MK-8931-016)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

21 molecules share ≥1 primary target. Top 21 by shared-target count:

Molecule	Source	Status	Shared targets
LANABECESTAT	ChEMBL	Phase 3	BACE1, BACE2
ATABECESTAT	ChEMBL	Phase 2	BACE1, BACE2
CHLOROQUINE	ChEMBL	Phase 4 (approved)	BACE1
CIANIDANOL	ChEMBL	Phase 4 (approved)	BACE1
DONEPEZIL	ChEMBL	Phase 4 (approved)	BACE1
GEFITINIB	ChEMBL	Phase 4 (approved)	BACE1
CAFFEIC ACID	ChEMBL	Phase 3	BACE1
CURCUMIN	ChEMBL	Phase 3	BACE1
ELENBECESTAT	ChEMBL	Phase 3	BACE1
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	BACE1
HYDROXYTYROSOL	ChEMBL	Phase 3	BACE1
PHLOROGLUCINOL	ChEMBL	Phase 3	BACE1
QUERCETIN	ChEMBL	Phase 3	BACE1
RUTIN	ChEMBL	Phase 3	BACE1
TYRAMINE	ChEMBL	Phase 3	BACE1
(+)-EPICATECHIN	ChEMBL	Phase 2	BACE1
(-)-EPICATECHIN	ChEMBL	Phase 2	BACE1
ACETOSIDE	ChEMBL	Phase 2	BACE1
ELLAGIC ACID	ChEMBL	Phase 2	BACE1
LUTEOLIN	ChEMBL	Phase 2	BACE1
SPICLOMAZINE	ChEMBL	Phase 2	BACE1