Activators & Inhibitors

17-AAG binds specifically to heat shock protein Hsp90 in a manner similar to geldanamycin, but the binding is weaker. Inhibits Akt activation and HER2 expression in tumor cells. Exhibits 100-fold higher binding affinity for tumor-cell-derived hsp90 over that derived from normal cells. Inhibits angiogenesis.

Potent (Ki, 0.6 nM), specific and reversible proteasome inhibitor; no significant inhibitory activity against other enzymes or receptors. Bortezomib inhibits cell proliferation of H460 cells (human non-small cell lung cancer cell lines) with an IC50 of 0.1 µM and has been associated with suppresion of prostate cancer cell lines with an IC90 of 10 nM.

Monohydrochloride form of HA-1077. Inhibits a number of kinases, including ROCK I (IC50 = 10.7 µM), ROCK II (IC50 = 1.9 µM), MAPK1 (IC50 = 5 µM), and PKCRK2 (IC50 = 4 µM). Weaker inhibitor of PKC (IC50 = 425 µM) and MLCK (IC50 = 95 µM) .

Dihydrochloride form of HA-1077. Inhibits a number of kinases, including ROCK I (IC50 = 10.7 µM), ROCK II (IC50 = 1.9 µM), MAPK1 (IC50 = 5 µM), and PKCRK2 (IC50 = 4 µM). Weaker inhibitor of PKC (IC50 = 425 µM) and MLCK (IC50 = 95 µM) .

Potent and selective inhibitor of phosphatidyl-inositol 3-kinase. Active in purified preparations and cytosolic fractions(IC50 = 5nM) and is highly cell permeable. Covalently binds to PI 3-kinase and is selective, inhibiting other kinases such as PI 4-kinase and myosin light chain kinase at concentrations 100-fold higher than that required for inhibition of PI 3-kinase.

Gefitinib is a tyrosine kinase inhibitor. It is a potent inhibitor of EGFR kinase (Ki = 0.40 nM), but much weaker against ErbB-2 kinase (Ki = 870 nM) and ErbB-4 kinase (Ki = 1.1 µM).

K252a is a general kinase inhibitor that inhibits PKA (Ki = 18 nM), PKC (Ki = 25 nM), PKG (Ki = 20 nM), CaMK (Ki = 1.8 nM), and phosphorylase kinase (IC50 = 1.7 nM). It functions by acting competitively with ATP and noncompetitively with the substrate.

Doramapimod is a protein kinase inhibitor with a >330-fold selectivity for p38 MAPK compared with 12 other protein kinases. Doramapimod prevents both the kinetic activity and phosphorylation of p38 MAPK by binding to the ATP pocket as well as to a novel allosteric binding site on p38 MAPK. Doramapimod also blocks proliferation of cells expressing BCR-ABL(T315I), with an IC50 of 2-3 µM.

Cediranib, also known as AZD2171, is a highly potent inhibitor of recombinant KDR tyrosine kinase activity in vitro (IC50 < 1 nM). Inhibitory activity was also observed against the kinase associated with Flt-1 (IC50 = 5 nM), the VEGF-C and VEGF-D receptor Flt-4 (IC50 ≤ 3 nM), recombinant PDGFR-related kinase c-Kit (IC50 = 2 nM), and PDGFRβ tyrosine kinase (IC50 = 5 nM). In HUVEC, it inhibited VEGF-stimulated phosphorylation of KDR, c-Kit, PDGFR-α, PDGFR-β in a dose-dependent manner with IC50 values of 0.5, 1, 5, and 8 nM, respectively. Cediranib exhibits antitumor and antiangiogenic activity, and is a potential treatment for hypertension.