Activators & Inhibitors

Activity: JNK3 inhibitor . Function/Pharmacology: Potent and selective JNK3 inhibitor. IC50 = 7nM and >2800-fold selective over p38.1 Cell permeable. Chemical Name: 3-(5-(3-m-Tolylureido)-1H-indazol-1-yl)-N-(3,4,5-trimethoxyphenyl)benzamide

Activity: Arginine methyl transferase 1 (PRMT1) inhibitor . Function/Pharmacology: Selective protein arginine methyltransferase 1 (PRMT1) inhibitor, IC50 = 1.5 μM. Displays no activity against CARM1 and Set7/9 methyltransferases. Inhibits growth of MCF7a breast cancer cells and LNCaP prostate cancer cells. Blocks androgen-induced gene expression in LNCaP cells1. Chemical Name: N,N’-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide)

Activity: SRPK inhibitor . Function/Pharmacology: Selective serine arginine protein kinase (SRPK) 1 inhibitor (Ki = 0.89 μM).1 Inhibits SRPK2 at higher concentrations. Does not significantly inhibit other SRPKs such as CLK1 and CLK4, or other classes of SR kinases. Inhibits viral replication by inhibition of host SR protein kinases.1 Modulates VEGF splicing to reduce pathological neovascularization in a rat model of retinopathy2 and controls VEGF-mediated tumor angiogenesis in xenografts3. Chemical Name: N-[2-(1-Piperidinyl)-5-(trifluoromethyl)phenyl]-4-pyridinecarboxamide

Activity: PARG inhibitor . Function/Pharmacology: A novel potent inhibitor of poly(ADP-ribose) glycohydrolase (PARG), IC50=1.7 μM1. Pre or post ischemia treatment (40 mg/kg) with GPI-16552 reduces brain infarct volumes in a rat model of cerebral ischemia2. It modulates the inflammatory response to ischemia/reperfusion in a rat splanchnic artery occlusion model3 and reduces the degree of spinal cord inflammation and tissue injury after experimental spinal cord trauma4. Synergizes with temozolomide in decreasing melanoma cell invasion and metastatic spreading in mice injected with B16 melanoma cells5. Chemical Name: N-bis-(3-Phenyl-propyl)-9-oxo-fluorene-2,7-diamide

Activity: Notch pathway inhibitor . Function/Pharmacology: FLI-06 was discovered in a screen designed to monitor the trafficking and processing of a ligand-independent Notch-enhanced GFP reporter. It disrupts the Golgi apparatus in a manner distinct from that of brefeldin A and inhibited general secretion at a step before exit from the ER which was accompanied by a tubule-to-sheet morphological transition of the ER and is thus a novel agent acting at an early stage in secretory traffic (EC50=2.3 M).1 Abolishes MFAP5-dependent transcriptional programs which are upregulated in intrahepatic cholangiocarcinoma.2 Suppresses proliferation and induces apoptosis in esophogeal squamous cell carcinoma cells.3

Activity: REV-ERBα agonist . Function/Pharmacology: Antagonist of the nuclear heme receptor, REV-ERB. Blocks the ability of the REV-ERBα agonist, GSK4112, to enhance REV-ERB-dependent repression in a cotransfection assay.1 Decreases glucagon secretion and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha cells.2 Enhances the expression of bone morphogenetic protein genes in rat uterus endometrium stromal cells.3 Shortens the period of circadian oscillations in mature granulosa cells stimulated with or without LH.4 Chemical Name: 1,2,3,4-Tetrahydro-2-[[5-(methylthio)-2-thienyl]carbonyl]-3-isoquinolinecarboxylic acid ethyl ester

Activity: ROS generator . Function/Pharmacology: Pyocyanine, a redox-active phenazine produced by P. aeruginosa and other pathogens, is an electron receptor, which stimulates redox cycling in bacteria as well as in a variety of human cell lines. It enhances oxidative metabolism, which increases the formation of intracellular reactive oxygen species (ROS) via reduction of NADPH. Pyocyanine accelerates neutrophil apoptosis in vitro. Pyocyanine production by P. aeruginosa suppresses the acute inflammatory response by pathogen-driven acceleration of neutrophil apoptosis and associated reduction of local inflammation. Chemical Name: 5-Methyl-1(5H)-phenazinone

Activity: HIF-2α antagonist . Function/Pharmacology: Potent and selective HIF-2α inhibitor, Kd=81 nM.1 Binds to the HIF-2α PAS-B domain2 and interferes with Hif-2α / ARNT heterodimerization reducing target gene expression in a cellular model1. Highly selective for HIF-2α displaying a >60-fold selectivity over HIF-1α.1,2 Chemical Name: N-(3-chloro-5-fluorophenyl)-4-nitro-2,1,3-benzoxadiazol-5-amine

Activity: Hepatocycte differentiation inducer . Function/Pharmacology: Enhances differentiation of induced pluripotent stem cells (iPSC) to hepatocytes. Promotes the maturation of iPSC-derived hepatocytes.1 Chemical Name: N,N’-(Methylene di-4,1-phenylene)bis-acetamide