Activators & Inhibitors

Activity: DUB inhibitor . Function/Pharmacology: PR-619 is a nonselective, reversible inhibitor of cysteine-reactive deubiquitinating enzymes (DUBs; 5-20 µM)1. PR-619 is highly useful for preserving ubiquitinated proteins during cell lysis. DUBs become unregulated in cell lysates and will act quickly to deubiquitinate proteins of interest during cell lysis. To preserve maximum amounts of ubiquitinated protein, include PR-619 (50-100 µM) in lysis buffers. PR-619 is also useful for interrogating the role of DUBs in intact cell systems2, and treatment of cells results in an overall accumulation of ubiquitinated proteins and many other phenotypes. Chemical Name: 2,6-Diaminopyridine-3,5-bis(thiocyanate)

Activity: GFRα1 agonist . Function/Pharmacology: A novel small molecule thought to be an agonist at the glial cell line-derived neurotrophic factor (GDNF) family receptor α-1 GFRα-1. It inhibits radiolabeled GDNF binding in Neuro-2A cells in a concentration dependent manner IC50=10.4 μM. Like GDNF, it induced Ret autophosphorylation and promoted neurite outgrowth in Neuro-2A cells1. Recent studies indicate that it enhances GFRα family receptor signaling in conjunction with ligand stimulation. Effective treatment for small-fiber neuropathy in mouse models of the disease.2,3 GDNF agonists may be a new class of Parkinson’s disease therapeutics.4 Chemical Name: (E)-N4-(7-chloro-2-(2-chlorostyryl)quinolin-4-yl)-N1,N1-diethylpentane-1,4-diamine 3(H3PO4)

Activity: BET bromodomain inhibitor . Function/Pharmacology: RVX-208 is a potent BET bromodomain antagonist with IC50 of 0.510 μM for BD2, with approximately 170-fold selectivity over BD11,2. Increases apolipoprotein A-1 and HDL cholesterol in vitro and in vivo3. Reduces atherosclerosis4. Chemical Name: 2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-4(3H)-quinzolinone

Activity: GSK-3b and CDK inhibitor . Function/Pharmacology: A potent GSK-3β inhibitor (IC50=22 nM)1. Also inhibits CDK1 (IC50=180 nM) and CDK5 (IC50=100 nM)1. Displays antimitotic properties and induces endoreplication following prophase arrest in HBL-100 cells2. Possesses antiangiogenic activity3. Attenuates β-amyloid-associated neuropathology in a mouse model of Alzheimer’s disease4. Cell permeable. Chemical Name: 3-[1,3-Dihydro-3-(hydroxyimino-2H-indol-2-ylidene]-1,3-dihydro-2H-indol-2-one

Activity: Cholesterol probe . Function/Pharmacology: Filipin III is a polyene macrolide antibiotic. It may be used in a double staining procedure for the detection of lipoproteins1. Binds specifically to cholesterol forming a fluorescent complex which may be used for staining2. Disrupts the lipid raft/caveolae endocytosis pathway3. Prevents pathological prion protein accumulation by reducing endocytosis and inducing cellular PrP release4. Chemical Name: From Streptomyces filipinensis

Activity: ALK5 inhibitor . Function/Pharmacology: Selective ALK5 inhibitor, IC50 = 59, 400 and 1400 nM for TGF-β RI, TGF-β RII and MLK-7K, respectively1. Inhibits Smad2 phosphorylation induced by TGF-β as well as fibronectin expression and MDA-MB-231 cell invasion2. Abolishes resistance of glioblastoma-initiating cells to radiation3. Cell permeable. Chemical Name: 4-(3-Pyridin-2-yl-1H-pyrazol-4-yl)quinolone

Activity: CARP-1 mimetic . Function/Pharmacology: CARP-1 functional mimetic. Interferes with CARP-1 binding to APC-2 (IC50=10-15 μM)1. Enhances CARP-1 expression and induces G2/M cell cycle arrest. Induces apoptosis and suppresses growth of medulloblastoma cells2 and malignant pleural mesothelioma cells3. Chemical Name: 1-[(2-Chlorophenyl)methyl]-5'-phenyl-spiro[3H-indole-3,2'(3'H)-[1,3,4]thiadiazol]-2(1H)-one

Activity: Cell viability probe . Function/Pharmacology: Renilla luciferase catalyzes coelentarazine oxidation by oxygen to produce light. Coelentarazine-h produces 10-fold higher light output than native coelentarazine. Coelentarazine-h also undergoes autoluminescence which is enhanced by superoxide anion and peroxynitrite in cells. May be used in gene reporter assays, live cell assays and biochemical assays (ELISA, BRET etc). Chemical Name: 2,8-Dibenzyl-6-(4-hydroxyphenyl)imidazole[1,2-a]pyrazin-3(7H)-one

Activity: ARE activator . Function/Pharmacology: Activator of antioxidant response element (ARE) which induces cytoprotective genes in human cells. It alkylates Keap1 at Cys151 and is reactive toward additional cysteines at higher concentrations. Disrupts Nrf2/Keap1 and Keap1/Cul3 interactions and stabilizes Nrf2. Activates ARE in an Nrf2 and PI 3-kinase dependent manner. Cell permeable and active in vivo. Chemical Name: 1-Chloro-6,7-dihydro-6,6-dimethyl-3-(methylsulfonyl)-benzo[c]thiophen-4(5H)-one