Elenbecestat

Summary

Elenbecestat (CHEMBL4204869) is a phase-3 clinical-stage small molecule targeting BACE1; indicated across 1 condition including alzheimer disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (BACE1)
• Indications: 1 condition
• Clinical trials: 12
• Chemistry: 437.4 Da · C19H18F3N5O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4204869
Name	Elenbecestat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	57827330
Molecular formula	C19H18F3N5O2S
Molecular weight	437.4
InChIKey	AACUJFVOHGRMTR-DPXNYUHVSA-N

SMILES: C[C@@H]1[C@H]2CSC(=N[C@]2(CO1)C3=C(C=CC(=C3)NC(=O)C4=NC=C(N=C4)C(F)F)F)N

IUPAC name: N-[3-[(4aS,5R,7aS)-2-amino-5-methyl-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-(difluoromethyl)pyrazine-2-carboxamide

Also known as: E-2609, E2609, Elenbecestat, ELENBECESTAT, Elenbecetat

Patent coverage: 77 distinct patent families (196 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 161 (82%) 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	Inhibition	8.15	0.1%	P56817

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Beta-secretase 1.

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 3 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BACE1	8.15	IC50	7	nM	CHEMBL_ACT_18996759
BACE1	7.57	Ki	27	nM	CHEMBL_ACT_24661389
BACE1	7.24	IC50	57	nM	CHEMBL_ACT_29193083

Target pathways

Aggregated over 1 target gene(s): BACE1.

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	1
membrane protein ectodomain proteolysis	1
response to lead ion	1
protein processing	1
amyloid-beta formation	1
swimming behavior	1
amyloid precursor protein catabolic process	1
positive regulation of neuron apoptotic process	1
amyloid-beta metabolic 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	3	MONDO:0004975	MONDO:0004975

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE1	10
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02956486	PHASE3	TERMINATED	A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer’s Disease
NCT02322021	PHASE2	TERMINATED	Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Participants With Mild Cognitive Impairment Due to Alzheimer’s Disease (Prodromal Alzheimer’s Disease) and Mild to Moderate Dementia Due to Alzheimer’s Disease
NCT01294540	PHASE1	COMPLETED	Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2609 in Healthy Subjects and an Elderly Cohort
NCT01511783	PHASE1	COMPLETED	Evaluation of the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of E2609 in Healthy Subjects
NCT01600859	PHASE1	COMPLETED	Evaluation of E2609 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer’s Disease (Study: E2609-A001-101 Amendment 02)
NCT01716897	PHASE1	COMPLETED	An Study to Determine the Bioavailability of E2609 Tablets Compared to Capsules and the Effect of Food on Absorption
NCT01975636	PHASE1	COMPLETED	An Open-label, Single Dose Study to Determine the Metabolism and Elimination of [14C]E2609 in Healthy Male Subjects
NCT02055703	PHASE1	COMPLETED	A 3-Part, Open-Label, Drug-Drug Interaction Study of Concomitant Administration of E2609 With Itraconazole, Rifampin, Digoxin, or Donepezil
NCT02207790	PHASE1	COMPLETED	Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2609 in Healthy Adult Male Japanese and White Subjects
NCT02222324	PHASE1	COMPLETED	A Study to Evaluate the Effects of E2609 on QTc Interval in Healthy Subjects
NCT02859207	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics of E2609 and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared With Healthy Subjects
NCT03055962	PHASE1	COMPLETED	Study to Evaluate the Safety and Tolerability of a Once Daily Dose of 50 mg E2609 in Healthy Japanese Subjects

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
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
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	BACE1
HYDROXYTYROSOL	ChEMBL	Phase 3	BACE1
LANABECESTAT	ChEMBL	Phase 3	BACE1
PHLOROGLUCINOL	ChEMBL	Phase 3	BACE1
QUERCETIN	ChEMBL	Phase 3	BACE1
RUTIN	ChEMBL	Phase 3	BACE1
TYRAMINE	ChEMBL	Phase 3	BACE1
VERUBECESTAT	ChEMBL	Phase 3	BACE1
(+)-EPICATECHIN	ChEMBL	Phase 2	BACE1
(-)-EPICATECHIN	ChEMBL	Phase 2	BACE1
ACETOSIDE	ChEMBL	Phase 2	BACE1
ATABECESTAT	ChEMBL	Phase 2	BACE1
ELLAGIC ACID	ChEMBL	Phase 2	BACE1
LUTEOLIN	ChEMBL	Phase 2	BACE1
SPICLOMAZINE	ChEMBL	Phase 2	BACE1