Activators & Inhibitors

Activity: Geldanamycin conjugate for affinity purification . Function/Pharmacology: A useful biotinylated ligand for affinity purification of HSP-90 and HSP-90- dependent client proteins. Chemical Name: null

Activity: HSP90 fluorescent probe . Function/Pharmacology: A novel geldanamycin fluorescent probe1 that may be used in a fluorescence polarization assay for HSP-90 inhibitors2,3. May also be used for detection of cell surface HSP-90 and for other applications. Fluorescent geldanamycin probes have been used to characterize geldanamycin drug-target interactions for effective translation of in vitro pharmacology to cellular and in vivo efficacy4. Chemical Name: null

Activity: RORag inverse agonist . Function/Pharmacology: A high affinity synthetic ligand for both RORα and RORγt acting as an inverse agonist. It binds specifically to the ligand-binding domain, inducing a conformational change which leads to diminished affinity for co-activators and increased affinity for co-repressors resulting in suppression of transcriptional activity1. It inhibits the development of murine TH17 cells2 and suppresses the expression of cytokines1. Suppresses insulitis and prevents hyperglycemia in a type 1 diabetes mouse model3. Protects against pathologic neovascularization in various mouse models of retinopathy4. Active in vivo Chemical Name: N-(5-(N-(4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)phenyl)sulphamoyl)-4-methylthiazol-2-yl)acetamide

Activity: Induces neuronal differentiation . Function/Pharmacology: Induces neuronal differentiation of multipotent hippocampal neural progenitor cells. It is more potent and selective compared to retinoic acid. Suppresses astrogliogenesis. Chemical Name: Ethyl 4-(methyl(2-phenylthiazol-4-yl)amino)benzoate

Activity: Clk family kinase inhibitor . Function/Pharmacology: Potent, ATP-competitive inhibitor of Clk-family kinases (IC50s = 15, 20 and 200 nM for mClk4, 1 and 2 respectively and >10 μM for mClk3)1. Also inhibits DYRK1A/B (IC50s = 24 and 34 nM respectively)2. Suppresses serine/arginine-rich protein phosphorylation, dissociation of nuclear speckles and Clk1/Sty-dependent alternative splicing in mammalian cells1. Affects the regulation of alternative splicing by phosphorylation of SR protein both in vitro and in vivo. Promotes skipping of exon 31 in the endogenous dystrophin gene3. Increases levels of Clk1/4 mature mRNAs by promoting splicing of the intron-retaining RNAs4. Chemical Name: (Z)-1-(3-Ethyl-5-methoxy-2,3-dihydrobenzothiazol-2-ylidene)propan-2-one

Activity: IKK inhibitor . Function/Pharmacology: BAY 11-7082 selectively inhibits TNF-induced phosphorylation of κ-α leading to decreased nuclear NF-κB and decreased adhesion molecule expression without affecting constitutive κ-α phosphorylation.1 The effects on adhesion molecule expression were found to be irreversible. Chemical Name: (E)-3-(4-Methylphenylsulfonyl)-2-propenenitrile

Activity: GPR-55 agonist . Function/Pharmacology: Endogenous cannabinoid. Weak ligand for CB1 (Ki = 23.8 μM) and CB2 (Ki = 13.9 μM) receptors. Inhibits fatty acid amide hydrolase (FAAH) ((IC50 = 5.1 μM). Modulates mast cell activation. Displays immunosuppressant, anti-inflammatory and anti-nociceptive activity. Chemical Name: N-(2-Hydroxyethyl)palmitamide

Activity: FAAH inhibitor . Function/Pharmacology: Potent and selective FAAH inhibitor. Initially forms a covalent adduct with FAAH but is slowly released, IC50 = 12 nM. 100-fold selectivity for FAAH-1 over FAAH-2. Cell permeable and active in vivo. Displays analgesic activity in various animal models. Chemical Name: 4-(3-Phenyl-[1,2,4]thizdiazol-5-yl)-piperazine-1-carboxylic acid phenylamide

Activity: FAAH inhibitor . Function/Pharmacology: A potent and selective irreversible FAAH inhibitor. Covalently modifies active site-serine (IC50=33 nM). Completely selective for FAAH relative to other mammalian serine hydrolases. Cell permeable Chemical Name: N-Phenyl-4-(quinolin-2-ylmethyl)piperazine-1-carboxamide