Rilpivirine

SKU: orb1224933

Description

A highly potent nonnucleoside inhibitor (NNRTI) of HIV-1 reverse trK7912:M7912anscriptase with IC50 of 0.4 nM for WT HIV-1 in cell-based assay; shows activity against a panel of single and double HIV-1 site-directed mutant (IC50=0.3-2 nM); orally active.HIV Infection Approved(In Vitro):R278474 is active against wild-type HIV-1 (EC50=0.4 nM) and all single and double mutants tested (EC50=0.1-2.0 nM).R278474 (10-5000 nM; 30 d) does not observe the sign of wild-type HIV-1 breakthrough at 1 μM within 30 days.R278474 inhibits 81% of clinical isolates (about 1200 recombinant clinical isolates) at a 50% inhibitory concentration (EC50) less than 1 nM, and inhibits 94% at EC50 less than 10 nM.TMC278 shows subnanomolar EC50s against wild-type HIV-1 group M isolates (0.07-1.01 nM) and nanomolar EC50s against group O isolates (2.88-8.45 nM) in MT4 T-cells.\n(In Vivo):R278474 (10-160 mg/kg; p.o. for 1 month) does not produce abnormal effects in rat, apart from liver weight increase and species-specific thyroid hypertrophy, both at the higher dose levels.R278474 (i.v.) exhibits elimination half-life ranges from 4.4 h in rat to 31 h in dog, and exposure (AUCinf) amounts to 3.1 μg h/mL (4 mg/kg) in rat, 8.7 μg h/mL (1.25 mg/kg) in dog, 1.4 μg h/mL (1.25 mg/ kg) in monkey, and 44 μg h/mL (1.25 mg/kg) in rabbit.R278474 (p.o.) exhibits half-life ranges between 2.8 h in rat and 39 h in dog, and oral bioavailability of 32% and 31% in rat and dog.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 500287-72-9
• MW: 366.4185
• Purity: >98% (HPLC)
• Formula: C₂₂H₁₈N₆
• SMILES: CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)/C=C/C#N
• Target: HIV
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  R278474 (10-160 mg/kg; p.o. for 1 month) does not produce abnormal effects in rat, apart from liver weight increase and species-specific thyroid hypertrophy, both at the higher dose levels. R278474 (i. v.) exhibits elimination half-life ranges from 4.4 h in rat to 31 h in dog, and exposure (AUCinf) amounts to 3.1 μg h/mL (4 mg/kg) in rat, 8.7 μg h/mL (1.25 mg/kg) in dog, 1.4 μg h/mL (1.25 mg/ kg) in monkey, and 44 μg h/mL (1.25 mg/kg) in rabbit. R278474 (p.o.) exhibits half-life ranges between 2.8 h in rat and 39 h in dog, and oral bioavailability of 32% and 31% in rat and dog.
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• In Vitro:
  R278474 is active against wild-type HIV-1 (EC50 = 0.4 nM) and all single and double mutants tested (EC50 = 0.1-2.0 nM). R278474 (10-5000 nM; 30 d) does not observe the sign of wild-type HIV-1 breakthrough at 1 μM within 30 days. R278474 inhibits 81% of clinical isolates (about 1200 recombinant clinical isolates) at a 50% inhibitory concentration (EC50) less than 1 nM, and inhibits 94% at EC50 less than 10 nM. TMC278 shows subnanomolar EC50s against wild-type HIV-1 group M isolates (0.07-1.01 nM) and nanomolar EC50s against group O isolates (2.88-8.45 nM) in MT4 T-cells.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

R 278474 | TMC 278 | TMC278 | TMC-278

Quick Database Links

Gene Symbol

HIV