Lanabecestat

Summary

Lanabecestat (CHEMBL3989948) is a phase-3 clinical-stage small molecule targeting BACE1; indicated across 3 conditions including alzheimer disease and liver disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (BACE1)
• Indications: 3 conditions
• Clinical trials: 18
• Chemistry: 412.5 Da · C26H28N4O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3989948
Name	Lanabecestat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	67979346
Molecular formula	C26H28N4O
Molecular weight	412.5
InChIKey	WKDNQONLGXOZRG-BOPKNSRXSA-N

SMILES: CC#CC1=CC(=CN=C1)C2=CC3=C(CC4([C@]35N=C(C(=N5)N)C)CCC(CC4)OC)C=C2

Also known as: AZD-3293, AZD3293, Lanabecestat, LY-3314814, LY3314814, LANABECESTAT, AZD 3293, LANABECESTAT (AZD3293), US8865911, 114, US8865911, 122, NA

Parent form; salt/anhydrous children: CHEMBL3989942

Patent coverage: 136 distinct patent families (338 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 316 (93%) 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	8.66	0.1%	P56817

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Amyloid-beta precursor protein, Beta-secretase 2, Beta-secretase 1.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
APP	9.85	IC50	0.14	nM	CHEMBL_ACT_27466421
BACE1	9.22	IC50	0.6	nM	CHEMBL_ACT_24661386
BACE1	8.92	IC50	1.2	nM	CHEMBL_ACT_17601962
APP	8.92	IC50	1.2	nM	CHEMBL_ACT_27466418
BACE1	8.92	IC50	1.2	nM	CHEMBL_ACT_27530393
BACE1	7.6	IC50	25	nM	CHEMBL_ACT_17601966
BACE1	7.58	Ki	26	nM	CHEMBL_ACT_18228359
BACE2	6.43	Ki	372	nM	CHEMBL_ACT_18228361

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

3 indications (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
liver disorder	1	MONDO:0005154	EFO:0001421
kidney failure	1	MONDO:0001106	HP:0000083

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
PHASE1	15
PHASE3	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02245737	PHASE2/PHASE3	TERMINATED	An Efficacy and Safety Study of Lanabecestat (LY3314814) in Early Alzheimer’s Disease
NCT02783573	PHASE3	TERMINATED	A Study of Lanabecestat (LY3314814) in Participants With Mild Alzheimer’s Disease Dementia
NCT02972658	PHASE3	TERMINATED	A Study of Lanabecestat (LY3314814) in Early Alzheimer’s Disease Dementia
NCT01739647	PHASE1	COMPLETED	A Single Dose Study to Assess the Safety, Effects, and Blood and Urine Drug Levels of AZD3293 in Healthy Subjects
NCT01795339	PHASE1	COMPLETED	A Two-part Multiple Dose Study to Assess the Safety and Effects of AZD3293 in Healthy Elderly and Alzheimer’s Patients
NCT02005211	PHASE1	COMPLETED	A Two-part Single and Multiple Dose Study to Assess the Safety , Pharmacokinetics and Effects of AZD3293 in Healthy Japanese Young and Elderly Volunteers
NCT02039180	PHASE1	COMPLETED	Relative Bioavailability Study to Assess Two Solid Formulations Compared to an Oral Solution of AZD3293 in Healthy Male and Non-Fertile Female Subjects
NCT02040987	PHASE1	COMPLETED	AZD3293 Thorough QT Study in Healthy Male Volunteers
NCT02126514	PHASE1	COMPLETED	A Phase I, Open-Label, Single-Center Study to Assess the Absorption, Metabolism, and Excretion of [14C]-AZD3293
NCT02406261	PHASE1	COMPLETED	A Drug-Drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants
NCT02540668	PHASE1	COMPLETED	A Drug Interaction Study of Lanabecestat (LY3314814) and Warfarin in Healthy Participants
NCT02568397	PHASE1	COMPLETED	A Drug-drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants
NCT02663128	PHASE1	COMPLETED	A Study of Lanabecestat (LY3314814) in Healthy Participants
NCT03019549	PHASE1	COMPLETED	A Study of Lanabecestat (LY3314814) in Healthy Participants When Taken With Rosuvastatin
NCT03222427	PHASE1	COMPLETED	A Study of LY3314814 in Healthy Participants
NCT03499041	PHASE1	WITHDRAWN	A Study of LY3314814 in Participants With Liver Impairment
NCT03506399	PHASE1	WITHDRAWN	A Study of Lanabecestat in Healthy Female Participants Taking Oral Contraceptive
NCT03545087	PHASE1	WITHDRAWN	A Study of Lanabecestat in Participants With Severe Kidney Impairment Compared to Healthy Participants

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
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
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