Activators & Inhibitors

Activity: PKG inhibitor . Function/Pharmacology: Selective protein kinase G inhibitor (Ki =0.23, 4 and >10 μM for PKG, PKC and PKA respectively1. Arrests human skin fibroblast cell cycle after the G0/G1 boundary2. Abolishes the cGMP-induced relaxation in smooth muscle cells (IC50=60 nM)3. Cell permeable. Chemical Name: null

Activity: Nuclear export inhibitor . Function/Pharmacology: Inhibitor of nuclear export of proteins. Acts via covalent binding to and inhibiting CRM1/exportin-11. Inhibits the nuclear export of the HIV regulatory protein Rev2. Stabilizes p53 by blocking its nuclear export3. Chemical Name: null

Activity: Transcription inhibitor . Function/Pharmacology: Inhibits DNA methyl transferase1. A selective Sp1 inhibitor, it binds to GC rich DNA sequences, displacing Sp1 transcription factor binding to oncogene promoters, inhibitings their expression2. Mithramycin A (at 10-200 nM) sensitizes tumor cells to TRAIL-induced apoptosis3. Chemical Name: null

Activity: Immunosuppressant prodrug . Function/Pharmacology: A mycophenolic acid prodrug. Immunosuppressive agent useful in prevention of organ allograft rejection.1 Is metabolized to mycophenolic acid in vivo which acts by inhibiting the biosynthesis of guanine nucleotides via inhibition of inosine 5’-monophosphate dehydrogenase, suppressing the production of proinflammatory cytokines, nitric oxide and LDH in macrophages.2,3 IL-2-dependent T cell proliferation is also inhibited.4 Inhibits microglial and astrocytic activation reducing cell death after neuronal injury.5 Active in vivo. Chemical Name: 6-(1,3-Dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid 2-(4-morpholinyl)ethyl ester

Activity: Immunosuppressant . Function/Pharmacology: Immunomodulator1. Blocks the biosynthesis of guanine nucleotides via inhibition of inosine 5’-monophosphate dehydrogenase which suppresses the production of proinflammatory cytokines, nitric oxide and LDH in macrophages2,3. Inhibits IL-2 -dependent T cell proliferation4. Chemical Name: 6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexanoic acid

Activity: Blocks sphingolipid biosynthesis . Function/Pharmacology: Myriocin is a fungal metabolite with potent immunosuppressant activity.1 It inhibits serine palmitoyltransferase (Ki = 0.28 nM) blocking the synthesis of ceramide.2 It was found to suppress melanoma cell proliferation by cell cycle arrest at the G 2/M phase through decreased sphingolipid levels and increased p53 and p21 (waf1/cip1) expression.3 Chemical Name: (2S,3R,4R,6E)-2-Amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxo-6-eicosenoic acid

Activity: Induces rapid intracellular acidification . Function/Pharmacology: Polyether ionophore which disrupts membrane potential and stimulates ATPase activity in mitochondria. Induces apoptosis resulting from intracellular acidification. Ion selectivity is K+> Rb+> Cs+>>Na+. Cell permeable. Chemical Name: null

Activity: Monovalent cation ionophore (K+ and NH4+) . Function/Pharmacology: Monovalent cation ionophore with high selectivity for NH4+ and K+1. Upregulates levels of mitochondrial stress proteins HSP58 and GRP752. Abolishes mitochondrial membrane potential3. Chemical Name: Isolated from Streptomyces griseus

Activity: Protein phosphatase PP2A inhibitor . Function/Pharmacology: A naturally occurring polyether marine toxin. Potent and selective inhibitor of protein phosphatases inhibiting PP2A completely at 1 nM and PP1 at higher concentrations, while PP2C is not inhibited. It is an extremely useful tool for studying cellular protein phosphorylation2. Induces apoptosis in a variety of cell types3. Activates atypical protein kinase isotypes and induces insulin-like effects in adipocytes4. Caution: SKIN IRRITANT, TUMOR PROMOTOR. Avoid contact. Chemical Name: Isolated from marine dionflagellates