Grazoprevir 是一种丙型肝炎病毒 NS3/4a 蛋白酶的选择性抑制剂，具有跨基因型和耐药变体的广泛活性，对 gt1b、gt1a、gt2a、gt2b 和 gt3a的Ki分别为 0.01 nM、0.01 nM、0.08 nM、0.15 nM 和 0.90 nM。它也是 SARS-CoV-2 3CLpro 抑制剂。

MK-5172 is a selective inhibitor of Hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants, with Ki of 0.01 nM (gt1a), 0.08 nM (gt2a), 0.90 nM (gt3a), 0.01 nM (gt1b), 0.15 nM (gt2b), respectively.

In biochemical assays, MK-5172 is effective against a panel of major genotypes and variants engineered with common resistant mutations, with Ki of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), 0.07 nM (gt1bR155K), 0.14 nM (gt1bD168V), 0.30 nM (gt1bD168Y), 5.3 nM (gt1bA156T), and 12 nM (gt1bA156V), respectively. In the replicon assay, MK-5172 demonstrates subnanomolar to low-nanomolar EC50s against genotypes 1a, 1b, and 2a, with EC50s of 0.5±0.1 nM, 2±1 nM, and 2±1 nM for gt1bcon1, gt1a, and gt2a, respectively. MK-5172 is potent against a panel of HCV replication mutants NS5A (Y93H) (EC50: 0.7 nM), NS5B nucleosides (S282T) (EC50: 0.3 nM), and NS5B (C316Y) (EC50: 0.4 nM)[1]. MK-5172 maintains the excellent potency against the gt 3a enzyme as well as a broad panel of mutant enzymes, has excellent potency in the replicon system [gt1b IC50(50% NHS): 7.4 nM; gt1a IC50(40% NHS): 7 nM], and shows excellent rat liver exposure[2].

When dosed to dogs, MK-5172 shows low clearance of 5 mL/min/kg and a 3 h half-life after iv dosing and has good plasma exposure (AUC: 0.4 μM/h) after a 1 mg/kg oral dose. Dog liver biopsy studies showed that the liver concentration of MK-5172 after the 1 mg/kg oral dose is 1.4 μM at the 24 h time point. Similar to its behaviour in rats, MK-5172 demonstrates effective partitioning into liver tissue and maintains high liver concentration, relative to potency, 24 h after oral dosing in dogs [2].

1350514-68-9

C38H50N6O9S

766.9

MK-5172

DMSO:25 mg/mL
Ethanol:15 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years