Activators & Inhibitors

Activity: Actin filament disrupting agent . Function/Pharmacology: A cell permeable fungal toxin which binds to the barbed end of actin, inhibiting its polymerization.1 Inhibits cell division, migration and glucose transport.2 Causes cell cycle arrest at G2/M and induces apoptosis in HCT-116 colorectal carcinoma cells.3 Cytochalasin B-induced membrane vesicles (CIMVs) retain cell surface receptors of the parent cells and retain fusion specificity with target cells.4 CIMVs are a promising new vector system for drug and biomolecule delivery due to their natural origin and participation in intercellular communication.5 Chemical Name: Fermentation product from Drechslera dematioidea

Activity: Adenylate cyclase activator . Function/Pharmacology: Forskolin is a widely used adenylate cyclase activator.1 It also is a positive inotropic agent, vasodilator and induces platelet activation among other activities.2-5 Chemical Name: 7β-Acetoxy-8,13-epoxy-1α,6β,9α-trihydroxylabd-14-en-11-one

Activity: VEGF R kinase inhibitor . Function/Pharmacology: Potent, reversible, selective inhibitor of VEGFR-2, also known as Flk-1 (IC50 = 700 nM). Inhibition of VEGFR-2 blocks angiogenesis in both in vitro and in vivo models. Cell permeable. Chemical Name: (E)-N-(3’’-Phenylpropyl)-α-cyano-3’,5’-diisopropyl-4’-hydroxycinnamamide

Activity: Immunomodulator . Function/Pharmacology: A fungal metabolite with immunosuppressive properties; blocks phagocytosis, cytokine production and proliferation of T and B cells.1 Inhibits chymotrypsin-like activity of 20S proteasome preventing IκBα degradation and preventing NF-κB degradation2. Displays antiinflammatory activity3 and blocks leukotriene B4 production via inhibition of LTA4 hydrolase4. It inhibits nuclear NOTCH2 and recovers a tumor-suppressor NOTCH3 activity in chronic lymphocytic leukemia cells.5 Chemical Name: (3R,5aS,6S,10aR)-2,3,5a,6-Tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-10H-3,10a-epidithiopyrazino [1,2-a]indole-1,4-dione;

Activity: Protein kinase C inhibitor . Function/Pharmacology: Natural product found in St. John’s Wort (Hypericum perforatum). A multifunctional agent that has been reported to be antidepressive, antineoplastic, antitumor and antiviral. Inhibitory effects have been demonstrated on various enzyme including MAO, PKC, dopamine-ß-hydroxylase, reverse transcriptase, telomerase and CYP.1 Hypericin can cause photosensitivity – as a result, it is being investigated as an agent in photodynamic therapy.2 Chemical Name: 1,3,4,6,8,13-Hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione

Activity: Calcium ionophore . Function/Pharmacology: Highly selective nonfluorescent calcium (Ca2+) ionophore.1 Induces a rapid rise in cytosolic Ca2+ in human neutrophils which is due to both release from cytosolic Ca2+ stores as well as Ca2+ influx.2 It activates (2 μM) and primes (20-200 nM) neutrophil NADPH oxidase2. Down regulates beta-catenin/Tcf signaling in a colon cancer cell line via suppressing the binding of Tcf to its specific DNA-binding site.3 In rat hepatoma cells, sub-lethal ionomycin activates the stress response by activating SAPK/JNK and HSF/HSE interaction leading to upregulation of HSP70 biosynthesis.4 Chemical Name: Fermentation product from Streptomyces conglobatus

Activity: Kinase inhibitor (pan-specific) . Function/Pharmacology: Potent pan-specific protein kinase inhibitor: PKA (Ki = 18 nM), PKC (Ki = 25 nM) PKG (Ki = 20 nM)1. Inhibits CaMK (Ki = 1.8 nM)2 and phosphorylase kinase (IC50 = 1.7 nM)3 as well as other kinases4. Induces apoptosis5. Cell permeable.

Activity: Kinase inhibitor (pan-specific) . Function/Pharmacology: Potent pan-specific protein kinase inhibitor: PKA (Ki = 90 nM), PKC (Ki = 20 nM), PKG (Ki = 100 nM)1 as well as other kinases. Cell impermeable2.

Activity: PKA inhibitor . Function/Pharmacology: Potent selective protein kinase A inhibitor: PKA (Ki = 60 nM). Displays no effect on PKC or PKG (Ki > 20 µM)1. Inhibits axon branching in cultured embryonic rat hippocampal pyramidal neurons2. Cell permeable.