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Chemical Structure| 1051375-10-0 Chemical Structure| 1051375-10-0

Structure of Cabotegravir
CAS No.: 1051375-10-0

Chemical Structure| 1051375-10-0

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Cabotegravir is a potent HIV integrase inhibitor as an oral lead-in tablet and long-acting injectable for the treatment and prevention of HIV infection. Cabotegravir is an inhibitor of OAT1 (IC50 0.81 μM) and OAT3 (IC50 0.41 μM).

Synonyms: GSK-1265744; S/GSK1265744; GSK1265744A

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Product Citations

Product Citations

Wood, Troy D ; Browne, Richard W ; Tiede, Erin R ; Gould, Connor E ; Ghazal, Diala ; DiFrancesco, Robin , et al.

Abstract: ISO/IEC 17043:2015 specifes general requirements for the competence of providers and development and operation of profciency testing schemes. As a requirement of ISO/IEC 17043:2015 accreditation, the Clinical Pharmacology Quality Assurance (CPQA) program uses ISO 17034 certifed reference materials (CRMs) to produce profciency testing materials in antiretroviral drug panels. CRMs that meet the ISO/IEC 17034 standard can be prohibitively expensive for CPQA participating laboratories (CPLs), requiring authentication of purity and identity by compendial testing. Here, to assist CPLs, we report on a compendial testing approach used to assess whether standard reference materials for bictegravir and cabotegravir, two commonly prescribed drugs used in combination regimens in the treatment of HIV-1 infection, for profciency testing. Our approach uses high-performance liquid chromatography and thermogravimetric analysis to evaluate purity of the materials, and the combination of high-resolution mass spectrometry and proton nuclear magnetic resonance spectroscopy to establish molecular identity. Using this workfow, we identifed standard reference materials for bictegravir and cabotegravir that are economical alternatives for CPLs.

Keywords: Bictegravir ; Cabotegravir ; Antiretroviral ; Profciency testing ; Quality assurance ; Metrology

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Product Details of Cabotegravir

CAS No. :1051375-10-0
Formula : C19H17F2N3O5
M.W : 405.35
SMILES Code : O=C(C1=CN(C2=C(O)C1=O)C[C@](OC[C@@H]3C)([H])N3C2=O)NCC4=CC=C(F)C=C4F
Synonyms :
GSK-1265744; S/GSK1265744; GSK1265744A
MDL No. :MFCD25976748

Safety of Cabotegravir

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Description
Cabotegravir (GSK-1265744) operates as an orally available, long-acting inhibitor of the HIV integrase strand transfer and the organic anion transporters 1 and 3 (OAT1/OAT3), with IC50s of 2.5 nM for HIVADA, 0.41 μM for OAT3, and 0.81 μM for OAT1. Its metabolism is mainly via the uridine diphosphate glucuronosyltransferase (UGT) 1A1, presenting minimal interaction risks with other antiretroviral drugs (ARVs), making it suitable for AIDS researc[1].[2].

In Vitro:

Cell Line
Concentration Treated Time Description References
CEMss cells 0.14 to 1.3 nM 6 days Assess the antiviral activity of Cabotegravir against HIV-2 in a spreading infection model, demonstrating high efficacy. PMC6153831
MeWo 0.5 µM and 3 µM 72 hours To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines. PMC10855363
FO-1 0.5 µM and 3 µM 72 hours To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines. PMC10855363
SK-Mel-28 0.5 µM and 3 µM 72 hours To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines. PMC10855363
A375 0.5 µM and 3 µM 72 hours To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines. PMC10855363
MAGIC-5A cells 1.2 to 1.7 nM (EC50) Evaluate the antiviral activity of Cabotegravir against HIV-1 and HIV-2, showing high efficacy against both viruses. PMC6153831

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Pregnancy model Oral gavage 0.5 mg/kg/day, 1.5 mg/kg/day, 5 mg/kg/day Once daily from gestational day 11.5 to 15.5 To determine the dose that would yield plasma drug concentrations similar to those observed in humans. Results showed that a 10× dose (5 mg/kg/day) of Cabotegravir resulted in a Cmax concentration of ~3500 ng/mL and a Cmin of ~1300 ng/mL, which are similar to those published in human pharmacokinetic studies. PMC9501129
Zebrafish Zebrafish embryos Immersion method 10-500 μM From gastrula stage (4 hpf) up to 120 or 144 hpf To assess the effects of Cabotegravir on zebrafish embryo development, including survival rate, morphological assessments, hatching rate, and neurotoxicity. Results showed that CAB at the highest concentrations caused pericardial edema, uninflated swim bladder, decreased heartbeats, growth delay, and decreased hatching rate. Decreased locomotion was observed even at the subtherapeutic dose, suggesting alterations of nervous system integrity. PMC9916638

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.47mL

0.49mL

0.25mL

12.34mL

2.47mL

1.23mL

24.67mL

4.93mL

2.47mL

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