WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 330045
CAS#: 2189684-44-2 (free base)
Description: Lenacapavir, also known as GS-6207, is a HIV-1 capsid inhibitor. Lenacapavir shows anti-HIV activity. Lenacapavir displays a mean EC50 of 50 pM (20-160 pM) against 23 HIV-1 clinical isolates from different subtypes in peripheral blood mononuclear cells (PBMCs). Lenacapavir demonstrated picomolar potency in vitro with no cross resistance to existing antiretroviral classes and potent antiviral activity in persons with HIV-1. In persons with HIV-1, there was no preexisting resistance to lenacapavir regardless of treatment history.
MedKoo Cat#: 330045
Name: Lenacapavir
CAS#: 2189684-44-2 (free base)
Chemical Formula: C39H32ClF10N7O5S2
Exact Mass: 967.1435
Molecular Weight: 968.283
Elemental Analysis: C, 48.38; H, 3.33; Cl, 3.66; F, 19.62; N, 10.13; O, 8.26; S, 6.62
Related CAS #: 2283356-18-1 (HCl) 2189684-44-2 (free base)
Synonym: Lenacapavir; GS-6207; GS 6207; GS6207; GS 714207; GS-714207; GS714207; GS-CA-2; GS-CA2; GS-HIV;
IUPAC/Chemical Name: N-((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide
InChi Key: BRYXUCLEHAUSDY-WEWMWRJBSA-N
InChi Code: 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
SMILES Code: FC1=CC(F)=CC(C[C@@H](C2=NC(C#CC(S(=O)(C)=O)(C)C)=CC=C2C3=CC=C(Cl)C4=C3N(CC(F)(F)F)N=C4NS(=O)(C)=O)NC(CN5C(C(F)(F)[C@@]6([H])[C@]7([H])C6)=C7C(C(F)(F)F)=N5)=O)=C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >3 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Lenacapavir (GS-6207) is a HIV-1 capsid inhibitor. |
| In vitro activity: | TBD |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 200.0 | 206.55 |
The following data is based on the product molecular weight 968.283 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | TBD |
| In vitro protocol: | TBD |
| In vivo protocol: | TBD |
1: Mushtaq A, Kazi F. Lenacapavir: a new treatment of resistant HIV-1 infections. Lancet Infect Dis. 2023 Mar;23(3):286. doi: 10.1016/S1473-3099(23)00075-0. PMID: 36841248.
2: Lenacapavir Sodium. Am J Health Syst Pharm. 2023 Feb 18:zxad018. doi: 10.1093/ajhp/zxad018. Epub ahead of print. PMID: 36801978.
3: Lee NE, Sutherland RK. Lenacapavir and the novel HIV-1 capsid inhibitors: an emerging therapy in the management of multidrug-resistant HIV-1 virus. Curr Opin Infect Dis. 2023 Feb 1;36(1):15-19. doi: 10.1097/QCO.0000000000000896. PMID: 36753704.
4: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. Lenacapavir. 2023 Jan 15. PMID: 36701515.
5: Chatzidaki I, Curteis T, Luedke H, Mezzio DJ, Rhee MS, McArthur E, Eddowes LA. Indirect Treatment Comparisons of Lenacapavir Plus Optimized Background Regimen Versus Other Treatments for Multidrug-Resistant Human Immunodeficiency Virus. Value Health. 2022 Dec 23:S1098-3015(22)04785-4. doi: 10.1016/j.jval.2022.12.011. Epub ahead of print. PMID: 36566886.
6: Orkin C. Lenacapavir in first-line therapy. Lancet HIV. 2023 Jan;10(1):e2-e3. doi: 10.1016/S2352-3018(22)00375-7. PMID: 36566080.
7: Gupta SK, Berhe M, Crofoot G, Benson P, Ramgopal M, Sims J, McDonald C, Ruane P, Sanchez WE, Scribner A, Liu SY, VanderVeen LA, Dvory-Sobol H, Rhee MS, Baeten JM, Koenig E. Lenacapavir administered every 26 weeks or daily in combination with oral daily antiretroviral therapy for initial treatment of HIV: a randomised, open-label, active-controlled, phase 2 trial. Lancet HIV. 2023 Jan;10(1):e15-e23. doi: 10.1016/S2352-3018(22)00291-0. PMID: 36566079.
8: Nka AD, Bouba Y, Teto G, Semengue ENJ, Takou DK, Ngueko AMK, Fabeni L, Carioti L, Armenia D, Pabo W, Dambaya B, Sosso SM, Colizzi V, Perno CF, Ceccherini-Silberstein F, Santoro MM, Fokam J, Ndjolo A. Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals. J Antimicrob Chemother. 2022 Dec 23;78(1):272-275. doi: 10.1093/jac/dkac388. PMID: 36411257.
9: Paik J. Lenacapavir: First Approval. Drugs. 2022 Sep;82(14):1499-1504. doi: 10.1007/s40265-022-01786-0. PMID: 36272024.
10: Bester SM, Adu-Ampratwum D, Annamalai AS, Wei G, Briganti L, Murphy BC, Haney R, Fuchs JR, Kvaratskhelia M. Structural and Mechanistic Bases of Viral Resistance to HIV-1 Capsid Inhibitor Lenacapavir. mBio. 2022 Oct 26;13(5):e0180422. doi: 10.1128/mbio.01804-22. Epub 2022 Oct 3. PMID: 36190128; PMCID: PMC9600929.
11: Margot NA, Naik V, VanderVeen L, Anoshchenko O, Singh R, Dvory-Sobol H, Rhee MS, Callebaut C. Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir. J Infect Dis. 2022 Nov 28;226(11):1985-1991. doi: 10.1093/infdis/jiac364. PMID: 36082606.
12: Cilento ME, Ong YT, Tedbury PR, Sarafianos SG. Drug Interactions in Lenacapavir-Based Long-Acting Antiviral Combinations. Viruses. 2022 May 31;14(6):1202. doi: 10.3390/v14061202. PMID: 35746673; PMCID: PMC9229705.
13: Marrazzo J. Lenacapavir for HIV-1 - Potential Promise of a Long-Acting Antiretroviral Drug. N Engl J Med. 2022 May 12;386(19):1848-1849. doi: 10.1056/NEJMe2204376. PMID: 35544391.
14: Segal-Maurer S, DeJesus E, Stellbrink HJ, Castagna A, Richmond GJ, Sinclair GI, Siripassorn K, Ruane PJ, Berhe M, Wang H, Margot NA, Dvory-Sobol H, Hyland RH, Brainard DM, Rhee MS, Baeten JM, Molina JM; CAPELLA Study Investigators. Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. N Engl J Med. 2022 May 12;386(19):1793-1803. doi: 10.1056/NEJMoa2115542. PMID: 35544387.
15: Troyano-Hernáez P, Reinosa R, Holguín Á. HIV Capsid Protein Genetic Diversity Across HIV-1 Variants and Impact on New Capsid-Inhibitor Lenacapavir. Front Microbiol. 2022 Apr 12;13:854974. doi: 10.3389/fmicb.2022.854974. PMID: 35495642; PMCID: PMC9039614.
16: Margot N, Vanderveen L, Naik V, Ram R, Parvangada PC, Martin R, Rhee M, Callebaut C. Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study. J Antimicrob Chemother. 2022 Mar 31;77(4):989-995. doi: 10.1093/jac/dkab503. PMID: 35028668.
17: Selyutina A, Hu P, Miller S, Simons LM, Yu HJ, Hultquist JF, Lee K, KewalRamani VN, Diaz-Griffero F. GS-CA1 and lenacapavir stabilize the HIV-1 core and modulate the core interaction with cellular factors. iScience. 2021 Dec 9;25(1):103593. doi: 10.1016/j.isci.2021.103593. PMID: 35005542; PMCID: PMC8718827.
18: Dvory-Sobol H, Shaik N, Callebaut C, Rhee MS. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. Curr Opin HIV AIDS. 2022 Jan 1;17(1):15-21. doi: 10.1097/COH.0000000000000713. PMID: 34871187.
19: Margot N, Ram R, Rhee M, Callebaut C. Absence of Lenacapavir (GS-6207) Phenotypic Resistance in HIV Gag Cleavage Site Mutants and in Isolates with Resistance to Existing Drug Classes. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02057-20. doi: 10.1128/AAC.02057-20. PMID: 33288639; PMCID: PMC8092519.
HIV-1 capsid inhibitors (of which lenacapavir is the first in class) has been postulated to have activity against multidrug resistant HIV-1 viral isolates. Initial results from the phase 3 trial CAPELLA (combining oral and subcutaneous lenacapavir alongside failing drug therapies) suggest that there may be a role for these novel agents in a cohort of patients living with HIV-1 infection (PLWH) for whom multidrug resistance has previously been a barrier to effective therapy.
