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
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
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2599 Sources: https://ard.bmj.com/content/75/Suppl_2/443.3 |
9.5 nM [IC50] | ||
Target ID: CHEMBL2366504 |
1.4 nM [Kd] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | SUNLENCA Approved UseSUNLENCA, 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 Date2022 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
1800 mg single, oral Highest studied dose Dose: 1800 mg Route: oral Route: single Dose: 1800 mg Sources: |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
|
927 mg single, subcutaneous Highest studied dose Dose: 927 mg Route: subcutaneous Route: single Dose: 927 mg Sources: |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
|
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 Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: |
Disc. AE: Injection site nodule... AEs leading to discontinuation/dose reduction: Injection site nodule (1, 1 pt) Sources: |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
PubMed
Title | Date | PubMed |
---|---|---|
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 |
Sample Use Guides
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
Sources: https://ard.bmj.com/content/75/Suppl_2/443.3
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
Edited
Tue Apr 01 22:26:01 GMT 2025
by
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on
Tue Apr 01 22:26:01 GMT 2025
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Record UNII |
A9A0O6FB4H
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Related Record | Type | Details | ||
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BINDER->LIGAND |
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SALT/SOLVATE -> PARENT |
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TARGET ORGANISM->INHIBITOR |
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METABOLIC ENZYME -> SUBSTRATE |
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EXCRETED UNCHANGED |
FECAL
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> INHIBITOR |
Moderate inhibitor
MINOR
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TARGET->INHIBITOR OF AGGREGATION |
Long acting drug
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Route of administration PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Route of administration PHARMACOKINETIC |
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