Activators & Inhibitors

Sorafenib Tosylate, also known as Bay 43-9006, is a novel bi-aryl urea compound that inhibits cell proliferation by targeting receptor tyrosine kinases, including VEGFR-2 and PDGFR-β and their associated signaling cascades of the ERK pathway and angiogenesis. It was originally developed as a Raf kinase inhibitor. It has been shown to have activity against several receptor tyrosine kinases involved in tumorigenesis and angiogenesis. Sorafenib is not active against erbB1, erbB2, ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-MET, c-yes, PKB, PKA, cdk1/cyclinB, PKC, or pim-1. Sorafenib has been shown to inhibit various nonkinase targets, including adenosine A3, dopamine D1, and muscarine M3 receptors, but at much higher (micromolar) concentrations than kinase targets. It is also the active ingredient in a drug that has been approved in at least one country for use in patients with advanced renal cell cancer. This version is NOT for human use.

Z-VAD(OMe)-FMK is a cell permeable, irreversible pan-caspase inhibitor and anti-apoptotic agent. It has been shown to inhibit Fas-mediated apoptosis in Jurkat T cells and apoptosis in THP.1 cells induced by diverse stimuli (including cycloheximide, thapsigargin, etoposide and staurosporine). Inhibits caspases 1, 3, 4, and 7.

Mocetinostat selectively inhibits histone deacetylases (HDACs) 1-3 and 11 at submicromolar concentrations. It blocks cancer cell proliferation in vitro and has significant antitumor activity in vivo. Mocetinostat induces hyperacetylation of histones, causes expression of the tumor suppressor protein p21(WAF1/CIP1), and inhibits proliferation of human cancer cells growing in culture.

Panobinostat, also known as LBH-589, is a highly active, non-selective HDAC inhibitor. IC50's against HDAC s 1-9 range between 3 - 61 nM except for a slightly higher IC50 value of 248 nM for HDAC 8. Panobinostat inhibits tumor cell proliferation and induces apoptosis in breast cancer and T cell lymphoma cells. In addition to its tumor-suppressive activities, panobinostat induces histone H3K9 and histone H4K8 acetylation and decreases the level of c-Myc expression.

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) .