Chemicals & Small Molecules

Telaprevir inhibits the hepatitis C virus NS3-4A serine protease, leading to the block of viral polyprotein processing. This eventually leads to a decrease of viral RNA replication, HCV RNA levels, as well as and protein levels in the Con1 (genotype 1b) subgenomic HCV replicon cells. This occurs in a time- and dose-dependent manner.

Danoprevir is a peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV) with an IC50 of 0.2-3.5 nM.

VX-222 is a novel, potent and selective inhibitor of non-nucleoside polymerase of the hepatitis C virus (HCV) RNA-dependent RNA polymerase, with an IC50 range of 0.94-1.2 µM. VX-222 selectively inhibits the replication of both HCV1a and HCV1b.

BMS-790052 is a highly selective and highly potent inhibitor of hepatitis C virus (HCV) NS5A. The mean EC50 values of BMS-790052 are 50 and 9 pM for HCV genotype 1a and 1b replicons, respectively. BMS-790052 is inactive towards a panel of 10 RNA and DNA viruses, with EC50 higher than 10 µM.

Orally active protease inhibitor. Known to inhibit trypsin and various inflammatory proteases including plasmin, kallikrein and thrombin.

PD 173074 inhibited the kinase activity of FGFR1 with an IC50 of 25 nM in vitro, while inhibiting Src, the receptors for insulin, epidermal growth factor (EGF) and PDGF, and several serine/threonine kinases with 1000-fold or higher IC50 values. PD 173074 was an ATP-competitive inhibitor of FGFR1, with a Ki of around 40 nM. PD 173074 inhibited autophosphorylation of FGFR1 and VEGFR2 in a dose-dependent manner with IC50s in the range of 1-5 nM and 100-200 nM, respectively.

A-769662 is a potent, reversible activator of AMP-activated protein kinase (AMPK). AMPK is an αβγ heterotrimer and plays an important role in regulating cellular and whole-body metabolism. A-769662 only activates AMPK heterotrimers containing the β1 subunit. A-769662 activates AMPK through the β subunit carbohydrate-binding module and the γ subunit but not the AMP-binding sites. A-769662 stimulated partially purified rat liver AMPK with an EC50 of 0.8 µM and inhibited fatty acid synthesis in primary rat hepatocytes with an IC50 of 3.2 µM.

PP242 is an inhibitor at the kinase domain of the mammalian target of rapamycin (mTOR), which is a Ser/Thr kinase and a cell growth controller. PP242 inhibits mTORC1 more effectively than rapamycin. Unlike rapamycin, PP242 inhibits both mTORC1 and mTORC2 with IC50 values of 0.03 and 0.058 µM, respectively and it can inhibit cap-dependent translation. PP242 functions by blocking the phosphorylation of Akt at S473 and preventing mTOR activation. PP242 exhitibits IC50 values for other kinases of 0.11 µM (JAK2), 0.41 µM (DNAPK), 0.05 µM (PKC?), 0.2 µM (PKCβ I and II), 4.4 µM (EGFR), and1.5 µM (VEGFR2).

Axitinib (AG-013736) is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), platelet derived growth factor receptor (PDGFR), and cKIT (CD117).