Activators & Inhibitors

Activity: PDGFR kinase inhibitor and Ox. phosphorylation inhibitor . Function/Pharmacology: Inhibits PDGF receptor tyrosine kinase (IC50 = 1.2 μM)1 and is a potent (10 nM) inhibitor of oxidative phosphorylation2. Inhibits cell growth by disrupting mitochondria3. Perturbs the golgi complex and blocks proliferation of vascular smooth muscle cells4. Chemical Name: 3,5-Di-tert-butyl-4-hydroxybenzylidene-malononitrile

Activity: Fn14 antagonist . Function/Pharmacology: Fn14 antagonist. Competes with TNF-like weak inducer of apoptosis (TWEAK) C-terminal/extracellular TNF homology domain (THD) for Fn14 binding (KD = 7.12 µM). It specifically inhibits TWEAK-Fn14-mediated NFκB activation. It completely suppressed TWEAK-induced T98G cell migration (10 μM) without cytotoxicity up to 50 μM1. L524-0366 is the first compound known to interfere with the TWEAK/Fn14 inter-action and may serve as a lead compound for the development of new therapeutics2. Chemical Name: (1-(3-Chlorophenyl)-1H-1,2,3-triazol-4-yl)(thiomorpholino)methanone

Activity: Glutaminase C inhibitor . Function/Pharmacology: Allosteric inhibitor of glutaminase C (GAC).1 Inhibition of GAC blocks oncogenic transformation induced by Rho GTPases in fibroblasts and B lymphoma cells with no effect on normal cells.2 Inhibits liver-type glutaminase GLS2 and suppresses breast tumor growth in vivo.3,4 Reverses acquired erlotinib resistance in non-small cell lung cancer.5 Chemical Name: 5-(3-bromo-4-(dimethylamino)phenyl)-2,2-dimethyl-2,3,5,6-tetrahydrobenzo[a]-phenanthridin-4(1H)-

Activity: Integrated stress response inhibitor . Function/Pharmacology: Integrated stress response inhibitor. Potently reverses the effects of initiation factor 2α (eIF2α) phosphorylation, IC50=5 nM.1 Enhances spatial and fear-associated learning in mice and enhances cognitive function.1,2 Mechanism of action involves activation of eiF2β.3 Suppresses ER stress-induced inflammatory gene expression.4 Potently attenuates amyloid β-induced neuronal cell death (12.5-25 nM) with no effect on amyloid β production.5 Reverses hippocampal-dependent cognitive deficits induced by traumatic brain injury in two different injury mouse models.6 Chemical Name: N.N’-trans-1,4-Cyclohexanediylbis[2-(4-chlorophenoxy)acetamide

Activity: PPARδ agonist . Function/Pharmacology: Potent and selective PPARδ (NR1C2) agonist, EC50=1.2 nM and 1000-fold selective over other PPAR subtypes.1 Induces apolipoprotein A1-mediated cholesterol efflux in vitro.1 Improves hematopoietic stem cell maintenance.2 Prevents downregulation of AMPK caused by a high-fat diet in liver and increases fatty acid oxidation.3 Upregulates human Sirt1 via Sp1 activation.4 Along with exercise, GW-501516 synergistically increases running endurance.5 Chemical Name: 2-[2-Methyl-4-[[[4-methyl-2-[4-(trifluoromethyl)phenyl]-5-thiazoyl]methyl]thio]phenoxy]acetic acid

Activity: Mitotic kinesin Kif18A inhibitor . Function/Pharmacology: A selective, ATP-competitive and reversible inhibitor of mitotic kinesin Kif18A, IC50=1.7 M.1,2 Binds to an allosteric site near Kif18A loop 5 preventing a range of conformational changes thereby blocking motor function.3 Inhibits the differentiation of mouse bone marrow cells to dendritic cells.4 Suppresses the replication of influenza A virus, inhibiting activation of AKT, p38 MAPK, SAPK and RanBP3 leading to the prevention of nuclear export of viral ribonucleoprotein complexes. Greatly improves the viability of IAV-infected mice.5 Chemical Name: 4-Chloro-2-nitro-1-(phenylsulfonyl)-benzene

Activity: Omi/HtrA2 protease inhibitor . Function/Pharmacology: UCF-101 is a potent, specific, competitive, and reversible inhibitor of the pro-apoptotic, mitochondrial serine protease Omi/HtrA2 (IC50 = 9.5 μM for His-Omi134-458). Shows very little activity against various other serine proteases tested (IC50 ≥ 200 μM).1 Mitigates streptozotocin-induced cardiomyocyte dysfunction.2 Protects against cerebral oxidative injury and cognitive impairment in a rat model.3 Cell permeable. Chemical Name: Dihydro-5[[5-(2-nitrophenyl)-2-furanyl]methylene]-1,3-diphenyl-2-thioxo-4,6(1H,5H)-pyrimidinedione

Activity: Aquaporin 4 blocker . Function/Pharmacology: Aquaporin 4 channel blocker, IC50 = 3.1 μM.1 Reduces ischemic cerebral edema in a mouse model of focal cerebral ischemia using MRI.2 Increases regional cerebral blood flow as determined in wild-type and AQP-4 knockout mice.3 Reduces brain edema when administered after onset of ischemia in rat models.4 Chemical Name: N-1,3,4-thiadiazol-2-yl-3-pyridinecarboxamide

Activity: Peroxynitrite donor . Function/Pharmacology: A metabolite of mosidomine1 which spontaneously releases nitric oxide and superoxide anion which react to form peroxynitrite under physiological conditions.2 The presence of HEPES leads to the formation of hydrogen peroxide and while its absence leads to the formation of peroxynitrite.3 Inhibits platelet aggregation.4 Inhibits aggregation and toxicity of amyloid- in cellular assays.5 Chemical Name: Amino-3-morpholinyl-1,2,3-oxadiazolium chloride