Anacetrapib

Summary

Anacetrapib (CHEMBL1800807) is a phase-3 clinical-stage small molecule targeting CETP; indicated across 7 conditions including familial hypercholesterolemia and coronary artery disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (CETP)
• Indications: 7 conditions
• Clinical trials: 16
• Chemistry: 637.5 Da · C30H25F10NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1800807
Name	Anacetrapib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11556427
Molecular formula	C30H25F10NO3
Molecular weight	637.5
InChIKey	MZZLGJHLQGUVPN-HAWMADMCSA-N

SMILES: C[C@H]1[C@H](OC(=O)N1CC2=C(C=CC(=C2)C(F)(F)F)C3=CC(=C(C=C3OC)F)C(C)C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F

IUPAC name: (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[[2-(4-fluoro-2-methoxy-5-propan-2-ylphenyl)-5-(trifluoromethyl)phenyl]methyl]-4-methyl-1,3-oxazolidin-2-one

Also known as: Anacetrapib, MK-0859, MK0859, Anacetrpib, ANACETRAPIB, SID174007279, anacetrapib, AnacetrapibÊ, AnacetrapibÂ, Anacetrapib (MK-0859)

Patent coverage: 327 distinct patent families (854 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 853 (100%) 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
CETP	cholesteryl ester transfer protein	Inhibition	7.76	0.2%	P11597

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Nuclear receptor subfamily 1 group I member 2, Cholesteryl ester transfer protein.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CETP	7.77	IC50	17	nM	CHEMBL_ACT_23309033
CETP	7.76	IC50	17.2	nM	CHEMBL_ACT_6285949
CETP	7.76	IC50	17.2	nM	CHEMBL_ACT_7995015
CETP	7.75	IC50	18	nM	CHEMBL_ACT_18143901
CETP	7.47	IC50	33.8	nM	CHEMBL_ACT_18312994
CETP	7.44	IC50	36	nM	CHEMBL_ACT_20600916
CETP	7.4	IC50	40	nM	CHEMBL_ACT_16810246
CETP	7.4	IC50	40	nM	CHEMBL_ACT_18002521
CETP	7.35	IC50	45	nM	CHEMBL_ACT_23308922
CETP	7.34	IC50	46	nM	CHEMBL_ACT_10855493
CETP	7.28	IC50	53	nM	CHEMBL_ACT_22483148
CETP	7.22	IC50	60	nM	CHEMBL_ACT_16491604
NR1I2	5.41	EC50	3900	nM	CHEMBL_ACT_23308974

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

7 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
familial hypercholesterolemia	3	MONDO:0005439	EFO:0004911
coronary artery disorder	3	MONDO:0005010	EFO:0001645
atherosclerosis	3	MONDO:0005311	EFO:0003914
hyperlipidemia	2	MONDO:0021187	MONDO:0021187

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

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE3	8
PHASE1	5
PHASE2	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01252953	PHASE3	ACTIVE_NOT_RECRUITING	REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification
NCT00685776	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01717300	PHASE3	COMPLETED	A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy (MK-0859-021)
NCT01760460	PHASE3	COMPLETED	A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy in Japanese Participants With Dyslipidemia (MK-0859-051 AM1)
NCT01824238	PHASE3	COMPLETED	A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy in Japanese Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-050)
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT01860729	PHASE3	COMPLETED	A Study of the Safety and Efficacy of Anacetrapib (MK-0859) Among Participants With Hypercholesterolemia When Added to Ongoing Statin Therapy (MK-0859-022)
NCT00325455	PHASE2	TERMINATED	MK0859 Dose-Ranging Study (0859-003)
NCT00977288	PHASE2	COMPLETED	A Study of Safety and Efficacy of MK0859 (Anacetrapib) in Japanese Patients With Dyslipidemia (0859-029)
NCT00565006	PHASE1	COMPLETED	A Study to Investigate the Influence of MK0859 on Blood Pressure (MK-0859-012)(COMPLETED)
NCT00565292	PHASE1	COMPLETED	A Study of MK0859 in Patients With Primary Hypercholesterolemia or Mixed Hyperlipidemia (MK-0859-011)(COMPLETED)
NCT00990808	PHASE1	COMPLETED	The Effect of MK0859 on Lipoprotein Metabolism in Patients With Dyslipidemia (0859-026 AM3)
NCT01114490	PHASE1	COMPLETED	Pharmacokinetics of Anacetrapib (MK0859) in Patients With Hepatic Insufficiency (MK-0859-039)
NCT01122667	PHASE1	COMPLETED	Pharmacokinetics of Anacetrapib (MK0859) in Subjects With Impaired Renal Function (MK-0859-038)
NCT02931188	Not specified	COMPLETED	The Effect of Anacetrapib on Vascular Function and Arterial Stiffness

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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
DALCETRAPIB	ChEMBL	Phase 3	CETP
EVACETRAPIB	ChEMBL	Phase 3	CETP
TORCETRAPIB	ChEMBL	Phase 3	CETP
URSOLIC ACID	ChEMBL	Phase 2	CETP