LENACAPAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C39H32ClF10N7O5S2
Molecular Weight	968.282
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C#CC1=CC=C(C(=N1)[C@H](CC2=CC(F)=CC(F)=C2)NC(=O)CN3N=C(C4=C3C(F)(F)[C@@H]5C[C@H]45)C(F)(F)F)C6=CC=C(Cl)C7=C6N(CC(F)(F)F)N=C7NS(C)(=O)=O)S(C)(=O)=O

InChI

InChIKey=BRYXUCLEHAUSDY-WEWMWRJBSA-N

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

HIDE SMILES / InChI

Molecular Formula	C39H32ClF10N7O5S2
Molecular Weight	968.282
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://pubmed.ncbi.nlm.nih.gov/36272024|https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf

Lenacapavir (Sunlenca®) is a long-acting capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) being developed by Gilead Sciences Inc. Lenacapavir is a multistage, selective inhibitor of HIV-1 capsid function that directly binds to the interface between capsid protein (p24) subunits in hexamers. Surface plasmon resonance sensorgrams showed dose-dependent and saturable binding of lenacapavir to cross-linked wild-type capsid hexamer with an equilibrium binding constant (KD) of 1.4 nM. Lenacapavir inhibits HIV-1 replication by interfering with multiple essential steps of the viral lifecycle, including capsid-mediated nuclear uptake of HIV-1 proviral DNA (by blocking nuclear import proteins binding to capsid), virus assembly and release (by interfering with Gag/Gag-Pol functioning, reducing production of capsid protein subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to malformed capsids). It is available as an oral tablet and injectable solution, with the latter being a slow-release formulation to allow bi-annual subcutaneous administration. In August 2022, lenacapavir received its first approval in the EU for use in combination with other antiretroviral(s) in adults with multi-drug resistant HIV infection, for whom it is otherwise not possible to construct a suppressive anti-viral regimen. On December 22, 2022 the US Food and Drug Administration granted approval for Gilead Sciences’ Sunlenca (lenacapavir) plus other antiretroviral(s) to treat human immunodeficiency virus type 1 infection.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase SYK 22 Target ID: CHEMBL2599 Sources: https://ard.bmj.com/content/75/Suppl_2/443.3	Inhibitor 8504		9.5 nM [IC50]
Structural capsid protein 2 Target ID: CHEMBL2366504 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf	Inhibitor 8504		1.4 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Human immunodeficiency virus type 1 (HIV-1) infection 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf	Primary		Approved 8583	SUNLENCA Approved Use SUNLENCA, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations. Launch Date 2022

C_max

Value	Dose	Co-administered	Analyte	Population
26.8 ng/mL OTHER https://www.hivandmore.de/kongresse/croi2021/slides/gilead/Jogiraju_LEN-PK-in-Hepatic-Impairment_CROI-2021_Poster-1315_Final.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LENACAPAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
9220 ng × h/mL OTHER https://www.hivandmore.de/kongresse/croi2021/slides/gilead/Jogiraju_LEN-PK-in-Hepatic-Impairment_CROI-2021_Poster-1315_Final.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LENACAPAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
314 h OTHER https://www.hivandmore.de/kongresse/croi2021/slides/gilead/Jogiraju_LEN-PK-in-Hepatic-Impairment_CROI-2021_Poster-1315_Final.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LENACAPAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.2% OTHER https://www.hivandmore.de/kongresse/croi2021/slides/gilead/Jogiraju_LEN-PK-in-Hepatic-Impairment_CROI-2021_Poster-1315_Final.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LENACAPAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1800 mg single, oral Highest studied dose Dose: 1800 mg Route: oral Route: single Dose: 1800 mg Sources: https://pubmed.ncbi.nlm.nih.gov/34871187/ https://journals.lww.com/co-hivandaids/Fulltext/2022/01000/Lenacapavir__a_first_in_class_HIV_1_capsid.4.aspx https://www.croiconference.org/wp-content/uploads/sites/2/posters/2020/1430_5_Begley_00470.pdf	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/34871187/ https://journals.lww.com/co-hivandaids/Fulltext/2022/01000/Lenacapavir__a_first_in_class_HIV_1_capsid.4.aspx https://www.croiconference.org/wp-content/uploads/sites/2/posters/2020/1430_5_Begley_00470.pdf	Sources: https://pubmed.ncbi.nlm.nih.gov/34871187/ https://journals.lww.com/co-hivandaids/Fulltext/2022/01000/Lenacapavir__a_first_in_class_HIV_1_capsid.4.aspx https://www.croiconference.org/wp-content/uploads/sites/2/posters/2020/1430_5_Begley_00470.pdf
927 mg single, subcutaneous Highest studied dose Dose: 927 mg Route: subcutaneous Route: single Dose: 927 mg Sources: https://pubmed.ncbi.nlm.nih.gov/34871187/ https://journals.lww.com/co-hivandaids/Fulltext/2022/01000/Lenacapavir__a_first_in_class_HIV_1_capsid.4.aspx https://programme.aids2020.org/Abstract/Abstract/8533	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/34871187/ https://journals.lww.com/co-hivandaids/Fulltext/2022/01000/Lenacapavir__a_first_in_class_HIV_1_capsid.4.aspx https://programme.aids2020.org/Abstract/Abstract/8533	Sources: https://pubmed.ncbi.nlm.nih.gov/34871187/ https://journals.lww.com/co-hivandaids/Fulltext/2022/01000/Lenacapavir__a_first_in_class_HIV_1_capsid.4.aspx https://programme.aids2020.org/Abstract/Abstract/8533
600 mg 1 times / day multiple, oral Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf#page=6 https://pubmed.ncbi.nlm.nih.gov/35544387/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf#page=6 https://pubmed.ncbi.nlm.nih.gov/35544387/	Disc. AE: Injection site nodule... AEs leading to discontinuation/dose reduction: Injection site nodule (1, 1 pt) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf#page=6 https://pubmed.ncbi.nlm.nih.gov/35544387/

AEs

AE	Significance	Dose	Population
Injection site nodule	1, 1 pt Disc. AE	600 mg 1 times / day multiple, oral Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf#page=6 https://pubmed.ncbi.nlm.nih.gov/35544387/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf#page=6 https://pubmed.ncbi.nlm.nih.gov/35544387/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 227 P-gp 1741 BCRP 910 UGT1A1 246 OATP1B1 1079 OATP1B3 961 OCT1 620 CYP2B6 926 OAT1 725 MATE2K 17 MATE1 415 CYP2C8 1057 OCT2 779 OAT3 747 CYP2C19 2057 CYP1A2 2153	UGT1A1 479 P-gp 2052 CYP3A 220 CYP2C8 810 CYP1A2 1197 CYP2B6 776 CYP2C19 1119 BCRP 697 OATP1B1 503 OATP1B3 435	CYP 74

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 327	moderate	yes (co-administration study) Comment: Co-administration increased midazolam Cmax by 1.94-fold and AUCinf by 2.59-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 327
CYP 150	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	unlikely
MATE2K 17	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	unlikely
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	unlikely
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	unlikely
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	unlikely
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327.0	unlikely
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327 \| 328	weak	no (co-administration study) Comment: Co-administration did not affect pitavastatin exposures (Cmax by 1.00-fold, AUCinf by 1.11-fold). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327 \| 328
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327 \| 328	weak	no (co-administration study) Comment: Co-administration did not affect pitavastatin exposures (Cmax by 1.00-fold, AUCinf by 1.11-fold). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 327 \| 328
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 327 \| 328	yes	weak (co-administration study) Comment: Co-administration increased rosuvastatin Cmax by 1.57-fold and AUCinf by 1.31-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 327 \| 328
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 327 \| 328	yes	weak (co-administration study) Comment: Co-administration increased tenofovir Cmax by 1.23-fold and AUCinf by 1.47. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 327 \| 328

Drug as victim

Target	Modality	Activity	Clinical evidence
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 324.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 320 \| 324 \| 325	yes	weak (co-administration study) Comment: Cobicistat increased Cmax by 2.10-fold and AUC by 2.28 fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 320 \| 324 \| 325
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 320 \| 324 \| 325	yes	yes (co-administration study) Comment: Cobicistat increased Cmax by 2.10-fold and AUC by 2.28 fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 320 \| 324 \| 325
UGT1A1 479	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 320 \| 324 \| 325	yes	yes (co-administration study) Comment: Atazanavir/cobicistat increased Cmax by 6.60-fold and AUC by 4.21-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215973,215974Orig1s000IntegratedR.pdf Page: 233 \| 320 \| 324 \| 325

PubMed

Title	Date	PubMed
Lenacapavir: a first-in-class HIV-1 capsid inhibitor.	2022 Jan 1	34871187
Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection.	2022 May 12	35544387
Lenacapavir for HIV-1 - Potential Promise of a Long-Acting Antiretroviral Drug.	2022 May 12	35544391
Lenacapavir: First Approval.	2022 Sep	36272024

Patents

Sample Use Guides

In Vivo Use Guide

Dosage of SUNLENCA: Initiation Day 1: 927 mg by subcutaneous injection (2 x 1.5 mL injections) 600 mg orally (2 x 300 mg tablets); Day 2: 600 mg orally (2 x 300 mg tablets); Dosage of SUNLENCA: Maintenance Every 6 months (26 weeks) a /-2 weeks 927 mg by subcutaneous injection (2 x 1.5 mL injections)

Route of Administration: Oral

In Vitro Use Guide

Lenacapavir inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells with EC50 values of 24–51 nM. Functionally, GS-9876 inhibits anti-IgM mediated CD69 and CD86 expression on B-cells (EC50=112±10 nM and 164±15 nM, respectively) and anti-IgM /anti-CD40 co-stimulated B cell proliferation (EC50=108±55 nM). In human macrophages, GS-9876 inhibits IC-stimulated TNFα and IL-1β release (EC50=121±77 nM and 9±17 nM, respectively). Anti-CD3/anti-CD28 stimulated T cell proliferation is weakly inhibited (EC50=1291±398 nM), with selectivity >10-fold versus the inhibition of B cell proliferation.

Substance Class	Chemical Created by `admin` on `Tue Apr 01 22:26:01 GMT 2025` Edited by `admin` on `Tue Apr 01 22:26:01 GMT 2025`
Record UNII	A9A0O6FB4H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GS-CA2

Preferred Name

English

LENACAPAVIR

Official Name

English

N-((1S)-1-(3-(4-CHLORO-3-(METHANESULFONAMIDO)-1-(2,2,2-TRIFLUOROETHYL)-1H-INDAZOL-7-YL)-6-(3-(METHANESULFONYL)-3-METHYLBUT-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-CYCLOPR

Systematic Name

English

1H-CYCLOPROPA(3,4)CYCLOPENTA(1,2-C)PYRAZOLE, N-((1S)-1-(3-(4-CHLORO-3-((METHYLSULFONYL)AMINO)-1-(2,2,2-TRIFLUOROETHYL)-1H-INDAZOL-7-YL)-6-(3-METHYL-3-(METHYLSULFONYL)-1-BUTYN-1-YL)-2-PYRIDINYL)-2-(3,5-DIFLUOROPHENYL)ETHYL)-5,5-DIFLUORO-3B,4,4A,5-TETRAHYD

Systematic Name

English

lenacapavir [INN]

Common Name

English

LENACAPAVIR [USAN]

Common Name

English

Lenacapavir [WHO-DD]

Common Name

English

GS6207

Code

English

GS-HIV

Common Name

English

GS-6207

Code

English

GS-CA-2

Code

English

GS-714207

Code

English

Code System Code Type Description

INN

11108