Cabotegravir

• CAT Number: I000281
• CAS Number: 1051375-10-0
• Molecular Formula: C19H17F2N3O5
• Molecular Weight: 405.35
• Purity: 98%
• Synonyms: GSK744; Cabotegravir; (3S,11aR)-N-(2,4-difluorobenzyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide
• Target: HIV integrase
• Target Protein: Q7ZJM1
• Solubility: DMSO: ≥ 12.67 mg/mL
• Appearance: Solid
• Storage: Dry, dark and at 2 - 8 °C for six months or -20°C for two years.
• IC50: IC50: 2.5 nM (HIVADA)
• IUPAC Name: (3R,6S)-N-[(2,4-difluorophenyl)methyl]-10-hydroxy-6-methyl-8,11-dioxo-4-oxa-1,7-diazatricyclo[7.4.0.03,7]trideca-9,12-diene-12-carboxamide
• InChI: InChI=1S/C19H17F2N3O5/c1-9-8-29-14-7-23-6-12(16(25)17(26)15(23)19(28)24(9)14)18(27)22-5-10-2-3-11(20)4-13(10)21/h2-4,6,9,14,26H,5,7-8H2,1H3,(H,22,27)/t9-,14+/m0/s1
• InChIKey: WCWSTNLSLKSJPK-LKFCYVNXSA-N
• SMILES: C[C@H]1CO[C@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O

Cabotegravir( Cat No.: I000281) is an integrase inhibitor medication that is used in combination with rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults who are virologically suppressed. Cabotegravir works by inhibiting the integrase enzyme, which is essential for the replication of the HIV virus. By inhibiting this enzyme, cabotegravir prevents the virus from inserting its genetic material into the DNA of human cells, thus slowing or halting the progression of the infection. Cabotegravir is administered by intramuscular injection every four weeks. It has been shown to be highly effective in clinical trials and is an important addition to the range of HIV treatment options available.

Overview of Clinical Research

Originator: Shionogi – GlaxoSmithKline (JV)
Developer: Gilead Sciences; National Institute of Allergy and Infectious Diseases; ViiV Healthcare
Class: Antiretrovirals; Fluorobenzenes; Oxazoles; Pyrazines; Pyridones; Small molecules
Mechanism of Action: HIV integrase inhibitors
Orphan Drug Status: No

Reference

1. Sci Transl Med. 2015 Jan 14;7(270):270ra5. doi: 10.1126/scitranslmed.3010297.
The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.
Radzio J(1), Spreen W(2), Yueh YL(2), Mitchell J(1), Jenkins L(1), García-Lerma JG(3), Heneine W(1).
Author information:
(1)Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. (2)GlaxoSmithKline, Research Triangle Park, NC 27709, USA. (3)Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. .
Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women.