Activators & Inhibitors

Specific inhibitor (IC50 = 1.40 µM) of phosphatidylinositol 3-kinase (PI3K).

Roscovitine is a potent inhibitor of p34cdc2 (IC50 = 0.2 µM). Also inhibits p33cdk2 and p33cdk5.

A cell-permeable, water-soluble, potent inhibitor of poly(ADP-ribose) polymerase (PARP; EC50 = 20 nM). Shown to be about 10,000 times more potent than the prototypical PARP inhibitor, 3-Aminobenzamide (Cat. No. 165350; EC50 = 200 µM). Does not act as an antioxidant at higher concentrations (1 µM to 10 mM). Exhibits neuroprotection in in vivo and in vitro models of stroke.

Specifically and reversibly blocks translocation of proteins from the endoplasmic reticulum to the Golgi apparatus and induces apoptosis in human tumor cells via caspase activation. Brefeldin A has been identified as an activator of the sphingomyelin signal transduction cycle.

Procaspase-activating compound; activates procaspase-3 to produce caspase-3 (EC50 = 0.22 µM). Also activates procaspase-7 in a less efficient manner (EC50 = 4.5 µM). Pro-apoptotic; induces apoptosis in both cancerous and non-cancerous cells dependent on procaspase-3 concentration (IC50 values are 0.003 - 1.41 and 5.02 - 9.98 µM respectively). PAC-1 had an IC50 value of 3 nM for induction of cell death, whereas in cells from adjacent normal tissue IC50 values of 3.2-8.5 µM were observed

Obatoclax, also known as GX15-070, is a novel Bcl-2 homology domain-3 (BH3) mimetic. It occupies a hydrophobic cleft within the BH3 binding groove of Bcl-2, antagonizing Bcl-2 and thus inducing apoptosis. Obatoclax inhibited primary acute myeloid leukemia (AML) progenitor cell proliferation with an average IC50 of 0.18 ± 0.07 µM, and it potently induced apoptosis in primary AML cells with an average IC50 of 3.6 ± 1.2 µM. Obatoclax overcomes Bcl-2-, Bcl-xL-, Bcl-w-, and Mcl-1-mediated resistance to BAX or BAK and to the proteasome inhibitor bortezomib.

BIIB021 is an orally available, synthetic small-molecule Hsp90 inhibitor. It binds in the ATP-binding pocket of Hsp90 (Ki = 1.7 ± 0.4 nM) and induces HER-2 degradation with an EC50 of 38 ± 10 nM in MCF-7 cells. It ncreases expression of the heat shock proteins Hsp90α and Hsp70, but has no effect on expression of the nonclient protein phosphatidylinositol 3-kinase p85 subunit. BIIB021 inhibits the proliferation of N87, MCF-7, and BT474 tumor cells with IC50 values of 0.06, 0.31, and 0.14 µM, respectively. It has significant antitumor activity in N87 stomach, BT474 breast, CWR22 prostate, U87 glioblastoma, SKOV3 ovarian, and Panc-1 pancreatic tumor xenograft models.

Potent inhibitor of protein phosphatases, especially the PP-1 and PP-2 classes, in numerous cell types. Non-phorbol type tumor promoter.

AICAR, also known as acadesine, is an adenosine regulating agent and AMPK activator. AICAR was found to activate AMP-activated protein kinase (AMPK) in skeletal muscle, inhibit acetyl-CoA carboxylase, reduce malonyl-CoA, and increase fatty acid oxidation and glucose uptake. Note: This product is not 5'-phosphorylated.