Activators & Inhibitors

Activity: NGFR kinase inhibitor . Function/Pharmacology: Inhibits NGF-induced neurite growth in PC12 cells via selective inhibition of NGF receptor(pp140c-trk) autophosphorylation (IC50 = 10 µM). No inhibition of EGF, or PDGF receptor phosphorylation at typical working concentrations. Chemical Name: 3,5-Di-t-butyl-4-hydroxybenzylidene cyanothioacetamide

Activity: JAK-2 inhibitor . Function/Pharmacology: A potent inhibitor of the JAK-2 tyrosine kinase. In acute lymphoblastic leukemia (ALL) cells, which abundantly express JAK-2, AG-490 dose-dependently blocked cell growth, induced apoptosis and inhibited DNA synthesis. Blocks the growth of all pre-B ALL cells with no effect on normal B or T cells. Does not significantly inhibit other kinases such as Lck, Lyn, Btk, Syk and Src. Reduces liver injury in LPS-induced shock3. A useful tool for exploring the role of JAK2/STAT3 pathway in physiologic processes4. Chemical Name: (E)-2-Cyano-3-(3,4-dihydrophenyl)-N¬-(phenylmethyl)-2-propenamide

Activity: AMPK activator . Function/Pharmacology: Activates AMP-activated protein kinase (AMPK). Promotes ligand-independent activation of the insulin receptor.1 Promotes skeletal muscle autophagy via activation of FoxO3a.2 Controls smooth muscle cell hyperproliferation in vascular disease.3 Induces osteogenic differentiation in mesenchymal stem cells.4 Inhibits proinflammatory response in glial cells.5 Cell permeable. Chemical Name: 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside

Activity: PDE5 inhibitor . Function/Pharmacology: Phosphodiesterase inhibitor (IC50=0.37, 0.38, 0.45, 0.9 and 4.5 μM for PDE11, 6, 10, 5 and 8 respectively.1,2 Potent equilibrative nucleoside transporter 1 (ENT1) inhibitor Ki=8.2 nM vs. 144.8 nM for ENT1 and ENT2 respectively.3 Antiplatelet activity.4 Chemical Name: 2,6-bis(Diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrimidine

Activity: Dopamine D2/D3 agonist . Function/Pharmacology: Dopamine D2 receptor agonist. Inhibits prolactin production3. Decreases cocaine self-administration in the rat4. Active in vivo. Chemical Name: (+)-2-Bromo-12’-hydroxy-2’-(1-methylethyl)-5’-(2-methylpropyl)-ergotaman-3’,6,’18-trione methanesulfonate

Activity: HSP90 inhibitor . Function/Pharmacology: Semi-synthetic analog of geldanamycin which is less toxic and more stable. Selectively binds to and inhibits HSP90 from tumor cells. Anti-angiogenic activity. Cell permeable. Chemical Name: 17-(Allylamino)-17-desmethoxygeldanamycin

Activity: 5-LO inhibitor . Function/Pharmacology: Zileuton is a reversible inhibitor (IC50 = 500nM RBL-1 cells, 300nM rat PMNL cells) of 5-Lipoxygenase (5-LO).1 It also inhibited leukotriene B4 biosynthesis (IC50’s = 400nM rat PMNL, 400nM human PMNL and 900nM human whole blood).1 Zileuton suppressed prostaglandin biosynthesis via interference with arachidonic acid release in macrophages independent of 5-LO inhibition (IC50 = 13 µM PGE2 inhibition in LPS-stimulated whole blood).2 Zileuton was approved by the FDA in 1997 for the treatment of asthma (ZYFLO). Chemical Name: N-(1-Benzo[b]thien-2-ylethyl)-N-hydroxyurea

Activity: Proteasome inhibitor . Function/Pharmacology: Specific inhibitor of the 20S proteasome chymotrypsin-like activity1. Inhibition of Brg1 proteasomal degradation by aclacinomycin A reverses (0.25 μM in ILU-18 cells ) the removal of Brg1 from promoters of inflammatory genes elucidating the regulatory role of the proteasome in controlling the duration of the inflammatory process2. Induces the differentiation of K562 cells towards the erythroid pathway3. Induces apoptosis4. Cell permeable.

Activity: Leukotriene CysLT1 antagonist . Function/Pharmacology: Competitive and selective leukotriene receptor antagonist1. Also inhibits calcium ionophore induced production of leukotriene B4 and leukotriene C4, which suggests a potential 5-LO inhibitory activity2. Cell permeable and orally active.