Dolutegravir

SKU: orb1300988

Description

Dolutegravir is a potent two-metal-binding HIV-1 integrase inhibitor with an IC50 of 2.7 nM. It demonstrates intermediate antiviral activity against key raltegravir-resistant mutants, including Y143R, Q148K, N155H, and G140S/Q148H. This small molecule is widely used in antiretroviral research for both in vitro mechanistic studies and in vivo efficacy models.

Research Area

Infectious Disease & Virology, Pharmacology & Drug Discovery, Protein Biochemistry

Key Properties

• CAS Number: 1051375-16-6
• MW: 419.38
• Purity: 98.97% (May vary between batches)
• Formula: C₂₀H₁₉F₂N₃O₅
• SMILES: C[C@@H]1CCO[C@H]2Cn3cc(C(=O)NCc4ccc(F)cc4F)c(=O)c(O)c3C(=O)N12
• Target: HIV Protease
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.87 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:84 mg/mL (200.3 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  HIV integrase:2.7 nM
• In Vivo:
  Following a single intravenous (IV) administration, Dolutegravir demonstrates low plasma clearance in rats (0.23 mL/min/kg) and monkeys (2.12 mL/min/kg), with a half-life of approximately 6 hours and a low steady-state volume of distribution (VSS). When orally administered as a solution to fasted male rats and a single monkey, Dolutegravir is rapidly absorbed, showing high oral bioavailability (75.6% and 87.0%, respectively). Dolutegravir exposure, assessed by peak concentration (Cmax) and area under the curve (AUC), increases with dose escalation in oral suspension forms up to 250 mg/kg in non-fasted rats and 50 mg/kg in non-fasted monkeys, albeit with a less than proportional increase.
• In Vitro:
  S/GSK1349572 shows the potent inhibitory effect on nine clinical isolates from integrase inhibitor-naive HIV-2-infected patients with EC50 ranging from 0.2 nM -1.4 nM. In vitro, S/GSK1349572 inhibits recombinant HIV-1 integrase-catalyzed strand transfer with IC50 of 2.7 nM. Furthermore, S/GSK1349572 potently inhibits HIV replication in cells such as peripheral blood mononuclear cells (PBMCs), MT-4 cells and CIP4 cells infected with a self-inactivating PHIV lentiviral vector with EC50 of 0,51 nM, 0.71 nM and 2.2 nM, respectively. In vitro, S/GSK1349572 exhibits potent activity against five different nonnucleoside reverse transcription inhibitor--resistant or nucleoside reverse transcription inhibitor--resistant viruses with EC50 ranging from 1.3 nM -2.1 nM. Similarly to that against wild-type virus, S/GSK1349572 shows equivalent activity against two protease inhibitor-resistant viruses with EC50 of 0.36 nM and 0.37 nM, respectively.
• Cell Research:
  MT-4 cells growing exponentially at a density of 500000 or 600000 /mL are infected with HIV-1 strain IIIB at a viral multiplicity of infection of 0.001 or a 50% tissue culture infective dose of 4 to 10. The cells are then aliquoted to 96-well plates in the presence of varying concentrations of S/GSK1349572. After incubation for 4 or 5 days, antiviral activity is determined by a cell viability assay that either measured bioluminescence with a CellTiter-Glo luminescent reagent or measured absorbance at 560 and 690 nm using the yellow tetrazolium MTT reagent [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide]. (Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Dolutegravir, inhibit, Inhibitor, Human immunodeficiency virus, HIVProtease, HIV, HIV integrase, HIV Integrase, HIV Protease, GSK 1349572, GSK1349572, GSK-1349572, S/GSK 1349572, S/GSK1349572, S/GSK-1349572

Compound Identifiers

PubChem CID

54726191