Activators & Inhibitors

Activity: PDE7 inhibitor . Function/Pharmacology: Potent and selective inhibitor of phosphodiesterase-7 (PDE7), Ki=180 nM1. Induces apoptosis in chronic lymphocytic leukemia cells which express PDE7B2. Increases mineralization in osteoblasts differentiated from hMSC3. Cell permeable. Chemical Name: 3-(N,N-Dimethylsulfonamido)-4-methylnitrobenzene

Activity: FAAH inhibitor . Function/Pharmacology: Potent and selective fatty acid amide hydrolase (FAAH) inhibitor, IC50 = 3-5 nM1. Produces cannabinoid CB1 and CB2 receptor-mediated analgesia in inflammatory pain states without causing side effects associated with cannabinoid receptor activation2. Attenuates the anxiolytic-like effect of acetaminophen in a mouse model3. Exerts anti-inflammatory effects in rat hippocampus and ameliorates age-related deficits4. Off target effects: Reduces tyrosine hydroxylase expression5. Chemical Name: Cyclohexylcarbamic acid 3’-(aminocarbonyl)-[1,1’-biphenyl]-3-yl ester

Activity: DUB inhibitor . Function/Pharmacology: Inhibits ubiquitin C-terminal hydrolase (UCH-L1) (Ki=0.4 M). Decreases proteasome activity and increases levels of ubiquitinated proteins. Induces apoptosis. Causes dramatic alterations in synaptic protein distribution and spine morphology in vivo. Cell permeable. Chemical Name: 5-Chloro-1-[(2,5-dichlorophenyl)methyl]-1H-indole-2,3-dione 3-(O-acetyloxime)

Activity: E1 UAE inhibitor . Function/Pharmacology: Inhibits ubiquitin activating enzyme E1 (>60% inhibition at 10 µM) with little or no activity against E2 or E3. Cell permeable Chemical Name: 4-[4-(5-Nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester

Activity: GTPase inhibitor . Function/Pharmacology: MLS-532223 is a high-affinity selective inhibitor of Rho family GTPases (EC50=10 μM). It inhibits EGF-stimulated Rac1 activation (3-10 μM). Cell permeable. Chemical Name: 1-(3-Nitrophenyl)-3-phenyl-2-propyn-1-one

Activity: HAT inhibitor . Function/Pharmacology: Potent and selective inhibitor of the histone acetyl transferase p300/CBP (Ki=400 nM ). Induces apoptosis in prostate cancer cells. Enhances fear extinction memory and synaptic plasticity in mice. Promotes tau deacetylation reducing levels of pathogenic p-tau. Cell permeable. Chemical Name: 4-[4-[[5-(4,5-Dimethyl-2-nitrophenyl)-2-furanyl]methylene]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzoic acid

Activity: Porcn inhibitor: Wnt/b-catenin pathway inhibitor . Function/Pharmacology: IWP-2 is an inhibitor of Wnt secretion and processing. It blocks Wnt-dependent signaling (IC50=27nM) by inhibition of the O-acyltransferase Porcn1. Induces cardiomyocyte differentiation from human pluripotent stem cells2. An important tool to probe the involvement of the Wnt pathway in physiological processes3,4. Cell permeable. Chemical Name: N-(6-Methyl-2-benzothiazolyl)-2-[(3,4,6,7-tetrahydro-4-oxo-3-phenylthieno[3,2-d]pyrimidin-2-yl)thio]-acetamide

Activity: Proteasome inhibitor . Function/Pharmacology: Specific inhibitor of the chymotrypsin-like activity of the 20S proteasome (IC50=100 nM with Z-LLL-AMC as substrate).1 Also inhibits calpain (IC50=1.25 μM)1 Suppresses gastric cancer cell proliferation and induces macro-autophagy2. Activates stress kinases and induces Hsp72.3 Induces neurite outgrowth.1 Blocks NFκB activation by blocking IκB proteolysis (IC50=3 μM).4 Cell permeable. Chemical Name: N-(Benzyloxycarbonyl)leucinylleucinylleucinal

Activity: AKT inhibitor . Function/Pharmacology: A novel ATP-competitive pan-specific Akt kinase inhibitor. (IC50’s=2, 13, 9 nM for Akt1, 2 and 3 respectively) Antitumor activity. Active in vivo. Induces hyperglycemia. Cell permeable. Chemical Name: (S)-4-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-(piperidin-3-ylmethoxy)-1H-imidazo[4,5-c]pyridine-4-yl)-2-methylbut-3-yn-2-ol · HCl