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enlicitide   Click here for help

GtoPdb Ligand ID: 13944

Synonyms: MK-0616 | MK0616
Compound class: Peptide
Comment: Enlicitide (MK-0616) is a macrocyclic peptide oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor [3]. PCSK9 is a dyslipidemia drug target. Enlicitide binds to PCSK9 and prevents its protein-protein interaction with the low-density lipoprotein receptor, which ultimately reduces plasma LDL-C concentration. Formulated as the chloride salt or decanoate adduct [7] for clinical use. The core peptide sequence is cyclo-Ala-D-Ala-Phe-Trp-Pro-Thr-Tyr-Pro-NH
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES C[C@H]1C(=O)N[C@H](CNC(=O)CCCCC[N+](C)(C)C)C(=O)N[C@H]2CC3=CC=CC(=C3)CNC(=O)CO[C@H]4CCN5[C@@H]4C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC6=CC=C(C=C6)OC)C(=O)N7CCC[C@@]7(C)C(=O)NCCC8=CC=C(C=C8)CN(CCCCCCN9C=C(C[C@@H](C5=O)NC2=O)C%10=C9C=CC(=C%10)F)C(=O)CCC(=O)N1
Isomeric 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)CC%10=CC=C(C=C%10)OC)[C@@H](C)O)CNC(=O)CCCCC[N+](C)(C)C
InChI InChI=1S/C82H109FN14O15/c1-51-74(103)91-65(47-86-68(99)19-11-10-14-40-97(4,5)6)76(105)88-62-43-56-17-15-18-57(41-56)46-85-70(101)50-112-67-33-39-95-73(67)78(107)92-72(52(2)98)77(106)90-63(42-54-24-27-60(111-7)28-25-54)80(109)96-38-16-34-82(96,3)81(110)84-35-32-53-20-22-55(23-21-53)48-94(71(102)31-30-69(100)87-51)37-13-9-8-12-36-93-49-58(44-64(79(95)108)89-75(62)104)61-45-59(83)26-29-66(61)93/h15,17-18,20-29,41,45,49,51-52,62-65,67,72-73,98H,8-14,16,19,30-40,42-44,46-48,50H2,1-7H3,(H8-,84,85,86,87,88,89,90,91,92,99,100,101,103,104,105,106,107,110)/p+1/t51-,52+,62-,63-,64-,65+,67-,72-,73-,82-/m0/s1
InChI Key ZJMSWDDEBKNMLX-HMPNVHCESA-O

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Ballantyne CM, Banka P, Mendez G, Garcia R, Rosenstock J, Rodgers A, Mendizabal G, Mitchel Y, Catapano AL. (2023)
Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616.
J Am Coll Cardiol, 81 (16): 1553-1564. [PMID:36889610]
2. Ballantyne CM, Gellis L, Tardif JC, Banka P, Navar AM, Asprusten EA, Scott R, Stroes ESG, Froman S, Mendizabal G et al.. (2026)
Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial.
JAMA, 335 (2): 129-139. [PMID:41206969]
3. Burnett JR, Hooper AJ. (2023)
MK-0616: an oral PCSK9 inhibitor for hypercholesterolemia treatment.
Expert Opin Investig Drugs, 32 (10): 873-878. [PMID:37815341]
4. Elbahloul MA, Gamal A, Elgendy IY. (2026)
The Oral PCSK9 inhibitor enlicitide for hypercholesterolemia.
Eur J Intern Med,: 106835 [Epub ahead of print]. [PMID:41833476]
5. Ferri N, Marodin G. (2025)
Emerging oral therapeutic strategies for inhibiting PCSK9.
Atheroscler Plus, 59: 25-31. [PMID:39802651]
6. Johns DG, Campeau LC, Banka P, Bautmans A, Bueters T, Bianchi E, Branca D, Bulger PG, Crevecoeur I, Ding FX et al.. (2023)
Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor.
Circulation, 148 (2): 144-158. [PMID:37125593]
7. Li H, Thaisrivongs DA, Shang G, Chen Y, Chen Q, Tan L, Xiao KJ, Larson RT, Kuethe JT, Lee J et al.. (2025)
Total Synthesis of Enlicitide Decanoate.
J Am Chem Soc, 147 (13): 11036-11048. [PMID:40123407]
8. Navar AM, Mikhailova E, Catapano AL, Banka P, Blom DJ, Cadena A, Kourpanidis S, Lepor NE, Tsukamoto K, Mendizabal G et al.. (2026)
A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide.
N Engl J Med, 394 (6): 529-539. [PMID:41879224]
9. Tomlinson B. (2026)
Pharmacological management of elevated LDL in patients with hypercholesterolemia and mixed dyslipidaemia.
Expert Opin Pharmacother, 27 (3): 211-225. [PMID:41782248]