Activators & Inhibitors

Activity: IRE1 ribonuclease inhibitor . Function/Pharmacology: A novel small molecule inhibitor of IRE1. It inhibits IRE1 endonuclease activity but not its kinase activity after endoplasmic reticulum stress1-3. It displays significant antimyeloma activity in model human MM xenografts1. Induces apoptosis in pancreatic cancer cells and displays growth inhibition in a clonogenic growth assay in soft agar as well as in a xenograft in vivo model of pancreatic cancer4. Active in vivo. Chemical Name: N-[(2-Hydroxy-1-naphthalenyl)methylene]-2-thiophenesulfonamide

Activity: RevErbα/β agonist . Function/Pharmacology: Agonist at nuclear receptor Rev-ErbA1. Greatly diminishes VILI-induced lung edema, inflammatory cell infiltration and TNFα production in a rat lung injury model2. Suppresses atherosclerosis in a mouse model3. Chemical Name: Ethyl 3-(((4-chlorobenzyl)((5-nitrophen-2-yl)methyl)amino)methyl)pyrrolidine-1-carboxylate hydrochloride

JNK3 inhibitor

Activity: SIRT 1&2 inhibitor . Function/Pharmacology: SIRT1 and SIRT2 inhibitor. Exhibits a stronger inhibitory effect on SIRT2 than on SIRT1 in vitro. Induces the reactivation of proapoptotic genes repressed by SIRT1 and causes massive apoptosis in cancer cells within 24 hours.1 Displays protective effect in nematodes expressing muscular dystrophy protein.2 Promotes neuronal apoptosis confirming the protective effect of SIRT1.3 Chemical Name: N-[3-[[(2-Hydroxy-1-naphthalenyl)methylene]amino]phenyl]-α-methylbenzeneacetamide

Activity: Calpain inhibitor . Function/Pharmacology: A selective, cell-permeable non-peptide calpain inhibitor (Ki for μ- and m-calpains = 0.21 and 0.37 μM respectively). Acts at the calcium binding site of calpain rather than the substrate-binding site. Inhibits calpain activity in two intact cell systems. Attenuates hypoxic/hypoglycemic injury to cerebrocortical neurons in culture and excitotoxic injury to Purkinje cells in cerebellar slices1. Displays cytoprotective effects in oxidant- and calcium ionophore-induced cell death2. Some protective effects may be due to inhibition of MMP activity3. Chemical Name: (Z)-3-(4-Iodophenyl)-2-mercapto-2-propenoic acid

Activity: GPR120 agonist . Function/Pharmacology: Potent and selective agonist at free fatty acid receptor 4 (FFA4), also known as GPR120. pEC50s= 6.3, 6.2 and 6.1 for human, mouse and rat receptor respectively1. Enhances glucose-stimulated insulin secretion in mouse insulinoma cells and induces intracellular calcium increase in U2OS osteosarcoma cells expressing GPR1202. Chemical Name: 4-Methoxy-N-(2,4,6-trimethylphenyl)benzenesulfonamide

Activity: CDK4 inhibitor . Function/Pharmacology: A novel marine natural product isolated from Thorectandra sp1. A potent and selective inhibitor of cyclin dependent kinase 4/cyclin D1 (IC50 = 0.35 μM) and is less selective for Cdk6/D1 (IC50 = 3.4 μM). Displays antiangiogenic acitivity2. Displays high cytotoxic activity against small cell lung cancer cell lines acting via multiple mechanisms including topoisomerase I, DNA integrity and ROS3. Chemical Name: 12,13-Dihydro-13-oxopyrido[1,2-a:3,4-b’]diindol-5-ium chloride

Activity: ATM Kinase inhibitor . Function/Pharmacology: Potent and selective ATM kinase inhibitor IC50s= 13, 2500, 9300, 16600, >100000 and >100000 nM for ATM, DNA-PK, mTOR, PI 3-kinase, PI 4-K and ATR respectively.1 Decreases viability of MCF-7, A549 and HCT116 cells and decreases p21CIP1 levels in vitro.2 Disruption of ATM signaling in primary A-T fibroblasts leads to dysregulation of ribonucleotide reductase and increase resistance to inhibitors of mitochondrial respiration and translation.3 Sensitizes radio-resistant cancer cells.4 Provides neuroprotection against H2O2-induced cell damage.5 Chemical Name: 2-(4-Morpholinyl)-6-(1-thiamthrenyl)-4H-pyran-4-one

Activity: GPR120 antagonist . Function/Pharmacology: Selective antagonist at free fatty acid receptor 4 (FFA4), also known as GPR120. pIC50s= 7.1 and <4.6 for FFA4 and FFA1 respectively. Inhibits linoleic acid and GSK137647A-induced intracellular calcium increase in U2OS osteosarcoma cells expressing GPR120.1 Has been used to probe the GPR120-mediated effects of fatty acids on a GnRH-synthesizing neuronal cell model.2 Chemical Name: 4-Methyl-N-9H-xanthen-9-yl-benzenesulfonamide