Activators & Inhibitors

Activity: KDM2/7 demethylase inhibitor . Function/Pharmacology: A selective inhibitor of the KDM2/7 JmjC subfamily of histone demethylases. IC50=1.5, 0.55 and 2.1 μM for KDM2A, PHF8 and KDM7A respectively. Highly selective over other subfamily members (KDM3, KDM4, KDM5 and KDM6) as well as other 2-oxoglutarate oxygenases (FIH, PHD2 and BBOX1), IC50>100 μM1. Chemical Name: 1-(2,2-Dimethylhydrazide)butanedioic acid

Activity: TrkB agonist . Function/Pharmacology: Small molecule BDNF mimetic displaying neurotrophhic activity. Partial agonist at TRKB and activates TRKB signaling. In in vitro models of neurodegenerative disease, it prevented neuronal degeneration with equal efficacy to that of BDNF. After in vivo administraton, it caused hippocampal and striatal TrkB activation in mice and improved motor learning after traumatic brain injury in rats1. Improves respiratory function in a mouse models of Rett syndrome2. Chemical Name: N,N’N’ Tris(2-hydroxyethyl)-1,3,5-benzenetricarboxamide

Activity: PICK1 PDZ domain inhibitor . Function/Pharmacology: The first small-molecule inhibitor of the PDZ domain in protein interacting with C kinase 1 (PICK1). Binds to PICK1 PDZ domain with affinity similar to that of the endogenous peptide ligands (Ki~10.1 µM). Does not bind to PDZ domains of postsynaptic density protein 95 (PSD-95) nor glutamate receptor interacting protein 1 (GRIP1). Pretreatment of cultured hippocampal neurons inhibits coimmunoprecipitation of the AMPA receptor GluR2 subunit with PICK1. FSC231 accelerated recycling of fluorophore-tagged GluR2 in hippocampal neurons after internalization in response to NMDA receptor activation. Blocks the expression of both long-term depression and long-term potentiation.1,2 Attenuates cocaine seeking in a rodent model.3 Blocks PICK1-induced anti-inflammatory effect in acute liver injury.4 Chemical Name: (E)-Ethyl-2-cyano-3-(3,4-dichlorophenyl)acryloylcarbamate

Activity: Src family kinase inhibitor . Function/Pharmacology: Potent and selective Src family kinase inhibitor. Inhibits Lck(IC50=4 nM); Fyn (IC50=5 nM); Hck (IC50=5 nM). It displays weak inhibition of EGFR (IC50=480 nM) and no inhibition of ZAP-70 (IC50> 100 μM) and JAK2 (IC50> 50 μM)1. It is a useful probe for exploring the involvement of Src family kinases in signal transduction pathways2. Chemical Name: 3-(4-Chlorophenyl)-1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Activity: PDE11 inhibitor . Function/Pharmacology: A potent and selective inhibitor of phosphodiesterase PDE11 (IC50=0.28 μM).1 IC50s for PDE1-10 are greater than 100 μM. Restores the ability of p54nrb / NONOKD cells to generate cAMP in response to ACTH stimulation and the production of cortisol and DHEA in response to cAMP signaling.2 Chemical Name: 6,7-Dihydro-3-phenyl-2-(propylthio)thieno[3,2-d]pyrimidin-4(3H)one

Activity: PLD assay standard . Function/Pharmacology: Phospholipase D converts phosphatidylcholine to phosphatidylethanol in the presence of ethanol. This reaction is the basis of a sensitive and selective assay for PLD activity in intact cells for which this product may be used as a chromatographic standard. Chemical Name: 1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphoethanol

Activity: Cryptochrome (CRY) activator . Function/Pharmacology: A novel tool that specifically interacts with cryptochrome (CRY) preventing its ubiquitin-dependent degradation resulting in lengthening of the circadian period. KL-001-mediated CRY stabilization inhibits glucagon-induced gluconeogenesis in primary hepatocytes1. Binds to the FAD-binding pocket of CRY2 as determined by co-crystal structure2. Induces an increase in period along with simultaneous reduction in amplitude of circadian reporter expression3 in mammalian cells. Chemical Name: N-[3-(9H-Carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)methanesulfonamide

Activity: Blocks importin-b-mediated nuclear import . Function/Pharmacology: Specifically inhibits importin-β-mediated nuclear import without disrupting transportin-mediated nuclear import or CRM1-mediated nuclear export1. When added to cells during mitosis it impairs the release of an importin- cargo probe and causes defects in spindle assembly. Inhibition of importin-β function is most likely mediated by blocking its interaction with RanGTP. It is an important new tool to probe the function of the importin-/RanGTP pathway2-4. Cell permeable Chemical Name: N-(1-Phenylethyl)-2-(pyrrolidin-1-yl)quinazolin-4-amine

Activity: TRPM8 blocker . Function/Pharmacology: Potent and selective inhibitor of TRPM8 channels. PBMC inhibits both chemical and thermal activation of TRPM81. Reverses the menthol and cold-induced facilitation of the micturition reflex2.Represents a new lead for analgesic drugs based on blocking TRPM83. Chemical Name: (S)-1-Phenylethyl(2-aminoethyl)(4-(benzyloxy)-3-methoxybenzyl)carbamate