Activators & Inhibitors

CI-994 is a histone deacetylase (HDAC) inhibitor that induces histone hyperacetylation. CI-994 inhibited HDAC-1 and HDAC-2 but not GCN5. CI-994 is also a novel antitumor agent, exhibiting activity against pancreatic, colon and mammary tumors. CI-994 inhibited the growth of two non-small cell lung cancer cell lines, A-549 (adenocarcinoma) and LX-1 (squamous cell carcinoma), with an IC50 of 80 µM.

Novel, potent and selective JNK-1,-2, and -3 inhibitor (Ki = 0.19 µM). SP600125 is an ATP-competitive reversible inhibitor with >20-fold selectivity vs. a range of kinases and enzymes tested. In cells, SP600125 caused a dose-dependent inhibition of the phosphorylation of c-Jun, the expression of inflammatory genes IL-2, COX-2, TNF-α, IFN-γ, and blocked the activation and differentiation of primary human CD4 cell cultures.

Temsirolimus, a rapamycin (sirolimus) derivative, also known as CCI-779, is an mTOR inhibitor with anti-cancer activity. Temsirolimus down-regulated the mTOR signaling intermediate phospho-S6 in xenografted human ALL. Temsirolimus has been shown to reverse cisplatin resistance in small cell lung cancer cell lines selected for cisplatin resistance and in cell lines derived from patients who failed cisplatin therapy.

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.

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) .

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.

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.