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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 of LENACAPAVIR

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

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

Targets

Primary TargetPharmacologyConditionPotency
9.5 nM [IC50]
1.4 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
26.8 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
9220 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
314 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.2%
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

Doses

DosePopulationAdverse events​
1800 mg single, oral
Highest studied dose
healthy, ADULT
927 mg single, subcutaneous
Highest studied dose
healthy, ADULT
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:
unhealthy, ADULT
Disc. AE: Injection site nodule...
AEs leading to
discontinuation/dose reduction:
Injection site nodule (1, 1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy, ADULT
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate
yes (co-administration study)
Comment: Co-administration increased midazolam Cmax by 1.94-fold and AUCinf by 2.59-fold.
Page: 233 | 327
no
no
no
no
no
no
no
no
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
weak
no (co-administration study)
Comment: Co-administration did not affect pitavastatin exposures (Cmax by 1.00-fold, AUCinf by 1.11-fold).
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).
Page: 327 | 328
yes
weak (co-administration study)
Comment: Co-administration increased rosuvastatin Cmax by 1.57-fold and AUCinf by 1.31-fold.
Page: 233 | 327 | 328
yes
weak (co-administration study)
Comment: Co-administration increased tenofovir Cmax by 1.23-fold and AUCinf by 1.47.
Page: 233 | 327 | 328
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
yes
weak (co-administration study)
Comment: Cobicistat increased Cmax by 2.10-fold and AUC by 2.28 fold.
Page: 233 | 320 | 324 | 325
yes
yes (co-administration study)
Comment: Cobicistat increased Cmax by 2.10-fold and AUC by 2.28 fold.
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.
Page: 233 | 320 | 324 | 325
PubMed

PubMed

TitleDatePubMed
Lenacapavir: a first-in-class HIV-1 capsid inhibitor.
2022 Jan 1
Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection.
2022 May 12
Lenacapavir for HIV-1 - Potential Promise of a Long-Acting Antiretroviral Drug.
2022 May 12
Lenacapavir: First Approval.
2022 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: oral, subcutaneous injection
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
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
  • Download
Name Type Language
GS-CA2
Preferred Name English
LENACAPAVIR
USAN   INN  
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
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
PUBCHEM
133082658
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
USAN
JK-52
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
DRUG BANK
DB15673
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
NCI_THESAURUS
C174616
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
DAILYMED
A9A0O6FB4H
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
FDA UNII
A9A0O6FB4H
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
CAS
2189684-44-2
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
SMS_ID
300000007900
Created by admin on Tue Apr 01 22:26:01 GMT 2025 , Edited by admin on Tue Apr 01 22:26:01 GMT 2025
PRIMARY
Related Record Type Details
BINDER->LIGAND
SALT/SOLVATE -> PARENT
TARGET ORGANISM->INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> SUBSTRATE
MINOR
METABOLIC ENZYME -> INHIBITOR
Moderate inhibitor
MINOR
TARGET->INHIBITOR OF AGGREGATION
Long acting drug
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC Route of administration
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC Route of administration
PHARMACOKINETIC