Evacetrapib

Summary

Evacetrapib (CHEMBL2017179) is a phase-3 clinical-stage small molecule targeting CETP; indicated across 4 conditions including cardiovascular disorder and hyperlipidemia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (CETP)
• Indications: 4 conditions
• Clinical trials: 25
• Chemistry: 638.6 Da · C31H36F6N6O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2017179
Name	Evacetrapib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	49836058
Molecular formula	C31H36F6N6O2
Molecular weight	638.6
InChIKey	IHIUGIVXARLYHP-UXNJHFGPSA-N

SMILES: CC1=CC(=C2C(=C1)[C@H](CCCN2CC3CCC(CC3)C(=O)O)N(CC4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)C5=NN(N=N5)C)C

IUPAC name: 4-[[(5S)-5-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-7,9-dimethyl-2,3,4,5-tetrahydro-1-benzazepin-1-yl]methyl]cyclohexane-1-carboxylic acid

Also known as: Evacetrapib, LY-2484595, LY2484595, EVACETRAPIB, evacetrapib, EVACETRAPIB (LY2484595), Evacetrapib (LY2484595)

Patent coverage: 117 distinct patent families (302 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
CETP	cholesteryl ester transfer protein	Inhibition	7.59	0.2%	P11597

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Cholesteryl ester transfer protein.

Bioactivity

ChEMBL activities: 2 potent at pChembl ≥ 5 of 2 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CETP	7.58	IC50	26	nM	CHEMBL_ACT_10855495
CETP	6.96	IC50	110	nM	CHEMBL_ACT_18143902

Target pathways

Aggregated over 1 target gene(s): CETP.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
LDL remodeling	1	CETP
HDL remodeling	1	CETP
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	CETP

Dominant GO biological processes

GO term	Targets
triglyceride metabolic process	1
lipid transport	1
cholesterol metabolic process	1
negative regulation of macrophage derived foam cell differentiation	1
regulation of cholesterol efflux	1
cholesterol transport	1
positive regulation of cholesterol transport	1
triglyceride transport	1
very-low-density lipoprotein particle remodeling	1
low-density lipoprotein particle remodeling	1
high-density lipoprotein particle remodeling	1
cholesterol homeostasis	1
reverse cholesterol transport	1
phosphatidylcholine metabolic process	1
lipid homeostasis	1

Indications & clinical

Indications

4 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
cardiovascular disorder	3	MONDO:0004995	EFO:0000319
hyperlipidemia	3	MONDO:0021187	MONDO:0021187

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 25.

Phase distribution

Phase	Trials
PHASE1	19
PHASE3	4
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01687998	PHASE3	TERMINATED	A Study of Evacetrapib in High-Risk Vascular Disease
NCT02227784	PHASE3	TERMINATED	A Study of Evacetrapib (LY2484595) in Participants With High Cholesterol
NCT02260635	PHASE3	TERMINATED	A Study of Evacetrapib (LY2484595) in Japanese Participants With Primary Hypercholesterolemia
NCT02260648	PHASE3	TERMINATED	A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia
NCT01105975	PHASE2	COMPLETED	A Study of LY2484595 in Patients With High LDL-C or Low HDL-C
NCT01375075	PHASE2	COMPLETED	A Study of LY2484595 in Japanese Subjects
NCT01448824	PHASE1	COMPLETED	A Study of LY2484595 on Pharmacokinetics in Healthy Participants
NCT01537887	PHASE1	COMPLETED	A Study of LY2484595 on the Electrical Activity of the Heart
NCT01736254	PHASE1	COMPLETED	A Study of Evacetrapib in Healthy Participants
NCT01746732	PHASE1	COMPLETED	A Study of Evacetrapib in Healthy Female Participants
NCT01810432	PHASE1	COMPLETED	Study of Food on Evacetrapib (LY2484595) in Healthy Participants
NCT01825876	PHASE1	COMPLETED	A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants
NCT01825889	PHASE1	COMPLETED	A Study of Evacetrapib (LY2484595) in Participants With Severe Renal Impairment and in Healthy Participants
NCT01836185	PHASE1	COMPLETED	A Study of Evacetrapib (LY2484595) in Participants With Hepatic (Liver) Impairment
NCT01897493	PHASE1	COMPLETED	A Study of Evacetrapib and Digoxin in Healthy Participants
NCT01903434	PHASE1	COMPLETED	A Study of Evacetrapib (LY2484595) in Healthy Participants
NCT01908582	PHASE1	COMPLETED	A Study of Evacetrapib and Rifampin in Healthy Participants
NCT01958489	PHASE1	COMPLETED	A Study of Evacetrapib in Japanese and Non-Japanese Participants
NCT02156492	PHASE1	COMPLETED	A Study of Evacetrapib With Selected Statins in Healthy Chinese Participants
NCT02161731	PHASE1	COMPLETED	Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants
NCT02168803	PHASE1	COMPLETED	A Study of Evacetrapib in Participants With Abnormal Cholesterol
NCT02226653	PHASE1	COMPLETED	A Study of Evacetrapib in Healthy Japanese Participants
NCT02271425	PHASE1	COMPLETED	A Study to Measure the Amount of Evacetrapib That Enters the Blood Stream in Healthy Participants
NCT02365558	PHASE1	COMPLETED	A Study to Evaluate the Effect of Increased Stomach pH on Evacetrapib in Healthy Participants
NCT02497391	PHASE1	COMPLETED	A Study of Different Particle Sizes of Evacetrapib in Healthy Participants

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

4 molecules share ≥1 primary target. Top 4 by shared-target count:

Molecule	Source	Status	Shared targets
ANACETRAPIB	ChEMBL	Phase 3	CETP
DALCETRAPIB	ChEMBL	Phase 3	CETP
TORCETRAPIB	ChEMBL	Phase 3	CETP
URSOLIC ACID	ChEMBL	Phase 2	CETP