Enlicitide

Summary

Enlicitide (CHEMBL6068773) is a phase-3 clinical-stage protein targeting PCSK9.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Protein
• Targets: 1 (PCSK9)
• Clinical trials: 12
• Chemistry: 1550.8 Da · C82H110FN14O15+

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL6068773
Name	Enlicitide
Type	Protein
Max phase	3
FDA approved	no
PubChem CID	164933665
Molecular formula	C82H110FN14O15+
Molecular weight	1550.8
InChIKey	ZJMSWDDEBKNMLX-HMPNVHCESA-O

SMILES: C[C@H]1C(=O)N[C@@H](C(=O)N[C@H]2CC3=CC(=CC=C3)CNC(=O)CO[C@H]4CCN5[C@@H]4C(=O)N[C@H](C(=O)N[C@H](C(=O)N6CCC[C@]6(C(=O)NCCC7=CC=C(CN(CCCCCCN8C=C(C[C@@H](C5=O)NC2=O)C9=C8C=CC(=C9)F)C(=O)CCC(=O)N1)C=C7)C)CC1=CC=C(C=C1)OC)[C@@H](C)O)CNC(=O)CCCCC[N+](C)(C)C

IUPAC name: [6-[[(11S,17S,20S,23S,27S,39S,42S,63S,66R)-47-fluoro-20-[(1R)-1-hydroxyethyl]-17-[(4-methoxyphenyl)methyl]-11,63-dimethyl-10,16,19,22,30,40,58,61,64,67,70-undecaoxo-28-oxa-1,9,15,18,21,24,31,41,51,62,65,68-dodecazanonacyclo[37.18.11.23,6.124,42.133,37.144,51.011,15.023,27.045,50]triheptaconta-3(73),4,6(72),33,35,37(71),44(69),45(50),46,48-decaen-66-yl]methylamino]-6-oxohexyl]-trimethylazanium

Parent form; salt/anhydrous children: CHEMBL6067978, CHEMBL6068420

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
PCSK9	proprotein convertase subtilisin/kexin type 9	Binding	11.3	4.6%	Q8NBP7

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 1 target gene(s): PCSK9.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	PCSK9
VLDLR internalisation and degradation	1	PCSK9
Post-translational protein phosphorylation	1	PCSK9
LDL clearance	1	PCSK9

Dominant GO biological processes

GO term	Targets
kidney development	1
liver development	1
negative regulation of receptor recycling	1
negative regulation of receptor internalization	1
positive regulation of receptor internalization	1
triglyceride metabolic process	1
phospholipid metabolic process	1
apoptotic process	1
lysosomal transport	1
cholesterol metabolic process	1
cellular response to starvation	1
negative regulation of low-density lipoprotein particle clearance	1
protein autoprocessing	1
neurogenesis	1
neuron differentiation	1

Indications & clinical

Indications

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE1	9
PHASE3	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07216482	PHASE3	RECRUITING	A Clinical Study of Enlicitide in Participants With High Cholesterol (MK-0616-037)
NCT06450366	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Enlicitide (MK-0616, Oral PCSK9 Inhibitor) Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia (MK-0616-018/CORALreef AddOn)
NCT07614984	PHASE2	NOT_YET_RECRUITING	A Clinical Trial of MK-7262 and Enlicitide in Participants With High Lipoprotein(a) (MK-7262-004)
NCT07300280	PHASE1	RECRUITING	A Clinical Trial of Enlicitide and Rosuvastatin in Healthy Adults (MK-0616-039)
NCT07481708	PHASE1	ACTIVE_NOT_RECRUITING	A Clinical Study of the Effect of Enlicitide (MK-0616) Formulations in Healthy Participants (MK-0616-041)
NCT06575959	PHASE1	COMPLETED	A Clinical Study of Enlicitide Decanoate in People With Liver Function Problems (MK-0616-030)
NCT06597760	PHASE1	COMPLETED	A Clinical Study to Assess the Effect of Enlicitide on How the Body Processes Digoxin in Healthy Adult Participants (MK-0616-031)
NCT06609512	PHASE1	COMPLETED	A Clinical Study of Enlicitide and the Effect of Food in Healthy Adult Participants (MK-0616-033)
NCT06643377	PHASE1	COMPLETED	A Clinical Study of Enlicitide in Participants With Severe Renal Impairment (MK-0616-032)
NCT06719544	PHASE1	COMPLETED	A Study of Lithium and Enlicitide in Healthy Adult Participants (MK-0616-034)
NCT06880874	PHASE1	COMPLETED	A Clinical Study to Evaluate Enlicitide (MK-0616) Formulations in Healthy Adult Participants (MK-0616-035)
NCT07044479	PHASE1	COMPLETED	A Clinical Study of How Coffee and Tea Affect Enlicitide in Healthy Volunteers (MK-0616-040)

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.

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

Molecule	Source	Status	Shared targets
NILOTINIB	ChEMBL + PubChem	Phase 4 (approved)	PCSK9