Dolutegravir Sodium (C09-0852-665)

Integrase inhibitors are a new class of antiretroviral drugs blocking the action of HIV integrase, which catalyses several key steps in the life cycle of the virus and is essential for insertion of the viral genome into the host cell DNA. GSK1349572 is a next-generation HIV integrase (IN) inhibitor.In vitro: GSK1349572 is a two-metal-binding HIV integrase strand transfer inhibitor whose mechanism of action was established through resistance passage experiments, integrase enzyme assays, mechanistic cellular assays and activity against viral strains resistant to other classes of anti-HIV agents. In a variety of cellular antiviral assays, GSK1349572 inhibited HIV replication with subnanomolar or low-nanomolar potency and with a selectivity index of 9,400. The protein-adjusted half-maximal effective concentration extrapolated to 100% human serum was 38 nM .In vivo: No animial in vivo data are available for GSK1349572 so far.Clinical trial: GSK1349572 was effective when given once daily without a pharmacokinetic booster and was well tolerated at all assessed doses. These findings support the assessment of once daily 50 mg GSK1349572 in phase 3 trials. Specification: 0.99 Molecular Formula: C20H18F2N3NaO5 Molecular Weight: 441.36 PubChem CID: 46216142 Isomeric SMILES: C[C@@H]1CCO[C@@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)[O-].[Na+]