Activators & Inhibitors

Activity: Promotes neuro-regeneration . Function/Pharmacology: A terpenoid, non-tumorigenic PKC activator isolated from Pimelia prostrate.1,2 Induces differentiation of human myeloid leukemia cells and potentiates differentiation by chemotherapeutic agents.3 Induces reactivation of latent HIV.4 Exerts a proliferative effect on neural progenitor cells in vitro and in vivo.5 Chemical Name: 13-O-Acetyl-12-deoxyphorbol

Activity: Biologically active glucose analog . Function/Pharmacology: 2-Deoxy-D-glucose (2-DG) is a synthetic glucose analog with extensive biological effects. It is commonly thought of as an inhibitor of glycolysis, but its metabolic effects are wide-ranging. 2-DG competitively inhibits glucose uptake via its metabolite 2-Deoxy-D-glucose-6-phosphate, which inhibits hexokinase and phosphoglucose-isomerase leading to decreased ATP production, cell cycle blockage, decreased cell growth and ultimately cell death.1,2 Chemical Name: null

Activity: p38 MAP kinase inhibitor . Function/Pharmacology: Potent and selective p38 MAP kinase inhibitor acting at the ATP site1. Selectively inhibits the p38α and β isoforms (IC50= 50 and 100 nM for SAPK2a/p38 and SAPK2b/p38β2 respectively)2. Effectively blocks LPS-induced gene expression in monocytes3. Induces apoptosis4. Cell permeable. Chemical Name: 4-[4-(4-Fluorophenyl)-5-(4-pyridiny¬l)-1H-imidazol-2-yl]phenol

Activity: p38 MAP kinase inhibitor . Function/Pharmacology: A potent and selective inhibitor of p38 MAP kinase, IC50=50 and 500 nM for p38 and p38β2 respectively. No other kinases (in a panel of 30) were significantly inhibited including p38γ and δ at 10 μM2. A potent inhibitor of inflammatory cytokine production (IC50=15-25 mg/kg in mice and rats) in animal models of arthritis, bone resorption, endotoxin shock and immune function3. Chemical Name: 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole

Activity: Raf-1 inhibitor (and other kinases) . Function/Pharmacology: Initially developed as a Raf kinase inhibitor, IC50 = 6 nM, but has been shown to inhibit many receptor tyrosine kinases including BRAF (IC50 = 22 nM); VEGFR-2 (IC50 = 90 nM); VEGFR-3 (IC50 = 20 nM); PDGFR-β (IC50 = 57 nM); Flt3 (IC50 = 58 nM); c-KIT (IC50 = 68 nM); FGFR-1 (IC50 = 580 nM)1. Paradoxically more potent in a cellular assay (IC50 = 20 nM) compared to an isolated enzyme assay (IC50 = 107 nM) for c-Fms2. Inhibits activation of MAPK pathway and ERK phosphorylation3. Induces caspase-independent apoptosis in melanoma cells4. Clinically useful anticancer agent. Chemical Name: 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylpicolinamide

Activity: JAK inhibitor . Function/Pharmacology: Potent pan-JAK inhibitor, IC50s=1, 20 and 112 nM for JAK3, JAK2 and JAK1 respectively.1 Displays potent antiinflammatory2 and immunosuppressant3 activity. Promotes a white-to-brown metabolic metabolic conversion in human adipoctes.4 In therapeutic use for rheumatoid arthritis.5 Chemical Name: null

Activity: Aurora kinase inhibitor . Function/Pharmacology: Inhibitor of Aurora kinases.1 Blocks cell cycle progressing, inhibits proliferation, and induces apoptosis in a wide range of cancer cell lines (IC50 = <10 μM for clear cell renal carcinoma).2,3 Chemical Name: null

Activity: Selective MEK1 and MEK2 inhibitor . Function/Pharmacology: Highly selective inhibitor of MEK1 and MEK2 in vitro and in vivo. Unlike PD98059, which only inhibits the activation of MEK1 and MEK2, U0126 inhibits both the active and inactive forms of the MEK enzymes. Inhibition of MEK1 and MEK2 has been demonstrated to enhance the self renewal of stem cells. Chemical Name: 1,4-Diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene

Activity: PI 3-kinase inhibitor . Function/Pharmacology: Novel Class I phosphatidylinositol 3-kinase (PI3K) inhibitor. ZSTK474 is an ATP-competitive inhibitor of all four Class I PI3K isoforms. However, it inhibits PI3Kδ most potently, with a Ki of 1.8 nM, while inhibiting the α, β and γ isoforms at slightly higher concentrations (6.7 nM, 10.4 nM and 11.7 nM, respectively)1. Displays potent antitumor activity against human cancer xenografts (A549, PC-3 and WiDr) when administered to mice2. It displays potent anti-inflammatory activity via modulation of human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis3. Ameliorates the progression of adjuvant-induced arthritis in a rat model4. Chemical Name: 2-(2-Difluoromethylbenzoimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine