Cabotegravir

Description: Cabotegravir / GSK1265744 / GSK744 is potent HIV integrase inhibitor under development for the treatment of HIV infection.

• Catalog: OFC1051375100
• CAS: 1051375-10-0
• Category: Fluorinated APIs
• Synonyms: GSK1265744
• Purity: >98%

• 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
• InChI Key: WCWSTNLSLKSJPK-LKFCYVNXSA-N
• Isomeric 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
• EC Number: 855-453-4

• Molecular Formula: C19H17F2N3O5
• Molecular Weight: 405.36
• Appearance: White to off-white solid powder

• XLogP3-AA: 2.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 3
• Exact Mass: 405.11362698 g/mol
• Monoisotopic Mass: 405.11362698 g/mol
• Topological Polar Surface Area: 99.2Ų
• Heavy Atom Count: 29
• Formal Charge: 0
• Complexity: 814

Case Study

Cabotegravir in Experimental Drug-Drug Interaction Studies with Morphine

Carbajal C, et al. Biomedicine & Pharmacotherapy, 2025, 184, 117925.

In a controlled murine study, cabotegravir was co-administered with morphine to evaluate potential drug-drug interactions mediated by uridine diphosphate glucuronosyltransferase (UGT) enzymes. Both male and female mice were treated with morphine alone or in combination with cabotegravir, followed by pharmacokinetic and pharmacodynamic assessments. Brain and liver tissues were analyzed for μ-opioid receptor expression, synaptic plasticity proteins, and inflammatory cytokine profiles. Quantification of morphine concentrations in the brain revealed enhanced analgesic effects in males when co-administered with cabotegravir, linked to altered UGT expression and disrupted drug metabolism. Histological and molecular assays demonstrated liver morphological changes and cytokine induction, particularly in males, alongside shifts in kidney excretion. This experimental model highlights cabotegravir's ability to modulate morphine biodistribution and immune-related pathways, providing critical insight into sex-specific drug interactions relevant to HIV therapy and opioid co-use.

Cabotegravir for the Application of Long-Acting Injectable HIV Therapy in Hemodialysis: A Two-Case Study

Hill KC, et al. Kidney Medicine, 2025, 7(9), 101060.

Two hemodialysis patients with suppressed HIV infection were transitioned from oral antiretroviral therapy to long-acting cabotegravir/rilpivirine (LA-CAB/RPV). Prior to switch, drug-drug interactions and resistance history were carefully reviewed. Transition followed standard intramuscular injection protocols, scheduled on non-dialysis days to avoid procedural overlap. No dose adjustment was required given the intramuscular depot formulation and high protein binding of cabotegravir. Patients underwent routine monitoring of HIV-1 RNA, CD4 count, renal panel, and tolerability at each maintenance visit. One patient continued LA-CAB/RPV through kidney transplantation with careful reconciliation of immunosuppressants. Both maintained durable viral suppression without injection-related or systemic adverse events. These cases experimentally demonstrate the feasibility of LA-CAB/RPV in end-stage kidney disease, highlighting its non-nephrotoxic profile and the clinical utility of long-acting regimens in patients with complex polypharmacy and dialysis dependence.