lenacapavir   Click here for help

GtoPdb Ligand ID: 11446

Synonyms: GS-6207 | GS6207 | Sunlenca®
Approved drug PDB Ligand
lenacapavir is an approved drug (EMA & FDA (2022))
Compound class: Synthetic organic
Comment: Lenacapavir (GS-6207) is a novel long-acting anti-HIV lead that binds to the virus' at a conserved interface between capsid protein monomers [2]. This mechanism disrupts early and late phases of the viral replication cycle [1] [3]. PDB entry 6V2F shows the crystal structure of lenacapavir-bound HIV capsid hexamer. In addition to being included in anti-HIV drug combinations, twice-yearly lenacapavir has already shown promising efficacy, and it is further being proposed as a once-yearly HIV prevention (preexposure prophylaxis; PrEP) candidate.

lenacapavir is commercially available from our sponsors

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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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were 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/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 10
Hydrogen bond donors 2
Rotatable bonds 14
Topological polar surface area 174.7
Molecular weight 967.14
XLogP 8.17
No. Lipinski's rules broken 2

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/)
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 O=C(Cn1nc(c2c1C(F)(F)[C@H]1[C@@H]2C1)C(F)(F)F)N[C@H](c1nc(C#CC(S(=O)(=O)C)(C)C)ccc1c1ccc(c2c1n(nc2NS(=O)(=O)C)CC(F)(F)F)Cl)Cc1cc(F)cc(c1)F
Isomeric SMILES O=C(Cn1nc(c2c1C(F)(F)[C@H]1[C@@H]2C1)C(F)(F)F)N[C@H](c1nc(C#CC(S(=O)(=O)C)(C)C)ccc1c1ccc(c2c1n(nc2NS(=O)(=O)C)CC(F)(F)F)Cl)Cc1cc(F)cc(c1)F
InChI InChI=1S/C39H32ClF10N7O5S2/c1-36(2,63(3,59)60)10-9-21-5-6-22(23-7-8-26(40)30-32(23)57(17-37(43,44)45)54-35(30)55-64(4,61)62)31(51-21)27(13-18-11-19(41)14-20(42)12-18)52-28(58)16-56-34-29(33(53-56)39(48,49)50)24-15-25(24)38(34,46)47/h5-8,11-12,14,24-25,27H,13,15-17H2,1-4H3,(H,52,58)(H,54,55)/t24-,25+,27-/m0/s1
InChI Key BRYXUCLEHAUSDY-WEWMWRJBSA-N

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/)
No information available.
Summary of Clinical Use Click here for help
Lenacapavir was advanced to Phase 2/3 clinical evaluation. First approval was granted by the EMA in August 2022, for the treatment of multi-drug resistant, and heavily pre-treated HIV infection (as a bi-annual subcutaneous injection). FDA approval for this indication followed in December 2022.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04143594 Study to Evaluate the Safety and Efficacy of Lenacapavir in Combination With Other Antiretroviral Agents in People Living With HIV Phase 2 Interventional Gilead Sciences
NCT04150068 Study to Evaluate the Safety and Efficacy of Lenacapavir in Combination With an Optimized Background Regimen in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance Phase 2/Phase 3 Interventional Gilead Sciences
NCT03739866 Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Lenacapavir Administered Subcutaneously in Human Immunodeficiency Virus (HIV) -1 Infected Adults Phase 1 Interventional Gilead Sciences 2
NCT06513312 Study of Lenacapavir Taken Twice a Year for HIV Pre-Exposure Prophylaxis (PrEP) Phase 2 Interventional Gilead Sciences
NCT04925752 Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection Phase 3 Interventional Gilead Sciences
External links Click here for help
For extended ADME data see the following:

European Medicines Agency (EMA)