Chemicals & Small Molecules

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.

NVP-AUY922 potently inhibits HSP90 with IC50 values of 7.8 nM and 21 nM, and Ki values of 9 nM and 8.2 nM for HSP90α and HSP90β, respectively. NVP-AUY922 shows a very high binding affinity to HSP90β with a Kd of 1.7 nM. NVP-AUY922 inhibits the proliferation of human tumor cells in vitro with GI50 values of approximately 2 to 40 nM, inducing G1-G2 arrest and apoptosis. Human endothelial cells are very sensitive to NVP-AUY922 with GI50s of 2.5-3.9 nM. NVP-AUY922 also exhibits potent antitumor efficacy in human tumor xenografts including BT474 breast, A2780 ovarian, U87MG glioblastoma, PC3 prostate, and WM266.4 melanoma.

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) .

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).