Activators & Inhibitors

Activity: PRMT3 inhibitor . Function/Pharmacology: Potent and selective allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3).1 IC50 = 31 nM and selective against 31 other methyltransferases. An extremely useful probe for investigating the role of PRMT3 in normal and pathophysiology. Cell permeable and active in vivo. Chemical Name: 1-Isoquinolin-6-yl-3-(2-oxo-2-pyrrolidin-1-yl-ethyl)-urea

Activity: Fatty acid synthase inhibitor . Function/Pharmacology: Potent and selective fatty acid synthase (FASN) inhibitor acting via interfering with cofactor binding.1 IC50s = 147 and 213 nM respectively for inhibition of acetate and glucose incorporation into total lipids in HepG2 cells. IC50=5.84 μM in an isolated enzyme assay. Displays potent antitumor activity in the MMTV-Neu HER2+ breast cancer model.1 Reduces HIV-1 virion production by 90% (EC50=213 nM).2 Chemical Name: 5,6-Dimethyl-N-[1-(phenylmethyl)-3-pyrrolidinyl]thieno[2,3-d]pyrimidin-4-amine benzenesulfonate hydrochloride

Activity: Spliceosome inhibitor . Function/Pharmacology: A novel polyketide fermentation product produced by Streptomyces chromofuscus, originally discovered by screening for herbicidal activity. Potent and selective inhibitor of spliceosome subunit SF3b.2 Specifically targets SAP155, a subunit of SF3b responsible for pre-mRNA splicing.3 Displays anti-angiogenic activity via down-regulation of VEGFR-2 and HIF-1α.4 Spliceosome inhibitors have attracted enormous attention due to their potential use in cancer treatment.5

Activity: Mitochondrial lipid messenger . Function/Pharmacology: A long-chain ceramide containing behenic acid. Mitochondrial-to-cytosolic stress response (MCSR) is a recently identified stress response which can be induced by increased synthesis of fatty acids. C22-ceramide is an endogenous signaling lipid which specifically inhibits MCSR with no effect on unfolded protein responses within the mitochondria.1 Hearts overexpressing Acyl CoA synthetase1 contain elevated levels of C22-ceramide.2

Activity: Leukemia cancer stem cell inhibitor . Function/Pharmacology: Inhibits leukemia stem cell (LSC) activity (EC50 = 200 nM). Displays a >100-fold selectivity for LSCs over normal hematopoietic stem cells.1 Chemical Name: N,N’-(Sulfonyldi-1,4-phenylene)bis[2,2,3,3-tetramethylcyclopropanecarboxamide]

Activity: RAD51 inhibitor . Function/Pharmacology: RI-1 is a potent and selective inhibitor of RAD51 (IC50 = 5-30 μM), a highly conserved protein that catalyzes DNA repair via homologous recombination.1 It specifically reduces gene conversion in human cells and stimulates single strand annealing. It covalently binds to Cys319 on the surface of RAD51 and disrupts protein-protein interaction. It potentiates the effect of DNA-damaging agents on tumor cells and is a novel tool for studying DNA repair in cells.2 Potentiates the killing of glioblastoma cells by ionizing radiation3 and alkylating drugs4. Chemical Name: 3-Chloro-1-(3,4-dichlorophenyl)-4-(4-morpholinyl)-1H-pyrrole-2,5-dione

Activity: pan-JUMONJI histone demethylase inhibitor . Function/Pharmacology: A novel specific inhibitor of the Jumonji family of histone demethylases in vitro, in cancer cells and in tumors in vivo. IC50 = 230, 340, 435, 445, 855 and 1100 nM for JARID1A, JMJD2E, JMJD2B, JMJD2A, JMJD3 and JMJD2C respectively. Reduces tumor burden and prolongs life in a mouse model.1 Suppresses translation initiation and enhances mTOR inhibitor sensitivity.2 Inhibits the growth of temozolomide-resistant glioblastoma cells and crosses the blood brain barrier.3 Chemical Name: (E)-5-Chloro-2-(2-(phenyl(pyridine-2-yl)methylene)hydrazinyl)pyridine

Activity: Adenylate cyclase 1 inhibitor, analgesic activity . Function/Pharmacology: A novel selective adenylyl cyclase 1 (AC1) inhibitor, IC50=2.3 μM . Inhibits calcium2+-stimulated cAMP accumulation in HEK cells stably transfected with AC11. It was also shown to inhibit AC1 stimulated by forskolin- and Gαs-coupled receptors in HEK-AC1 cells. It enhanced μ-opioid receptor-mediated inhibition of AC1 but it blocked heterologous sensitization of AC1 caused by chronic μ-opioid receptor activation.1 Displays analgesic properties in a mouse model of inflammatory pain.1 Chemical Name: 6-Chloro-2-(trichloromethyl)-4H-1-benzopyran-4-one

Activity: Novel cannabinoid CB2 agonist; antiinflammatory . Function/Pharmacology: Analog of the natural amides occurring in Echinacea which represent a new class of cannabinomimetic compounds. This class of compounds modulates TNFα mRNA expression in human monocytes/macrophages via the CB2 receptor.1 Dienamide A2 binds to cannabinoid receptors with greater affinity than endogenous cannabinoids (Ki= ~60 and >1500 nM for CB2 and CB1 respectively)2. It elevates intracellular Ca2+ levels in CB2-positive but not in CB2-negative cells and this effect was blocked by SR144528.2 It significantly inhibits LPS-induced TNFα and IL-1β expression in a CB2-independent manner.2 Chemical Name: (2E,4E)-N-Isobutyldodeca-2,4-dienamide