Activators & Inhibitors

Activity: HSP70 modulator . Function/Pharmacology: Acts as an artificial co-chaperone for HSP701. The activity of compound 115-7c mirrors those of HSP40 stimulating the ATPase and protein-folding activities of prokaryotic HSP70. Increases tau levels in cell lines overexpressing tau2. Induces solubilization of polyglutamine and exacerbates polyQ-mediated toxicity3,4. An important probe for understanding HSP70 functions4 Chemical Name: 4-(5-((Benzyloxycarbonyl)-4-(2,4-dichlorophenyl)-6-methyl-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)butanoic acid

Activity: B-Raf mutant inhibitor . Function/Pharmacology: Dabrafenib is a selective inhibitor of mutant B-RafV600E (IC50 = 0.8 nM), with 4- and 6-fold reduced potency against wild type B-Raf and c-Raf (IC50 = 3.2 and 5 nM, respectively).1 Has been in clinical trials in patients with B-RafV600E metastatic melanoma and other solid tumors. Endoplasmic reticulum stress and autophagy are induced in melanoma cells after treatment with dabrafenib and protect cells from dabrafenib toxicity.2 Induces epithelial differentiation in BRAF-mutant colorectal cancer cells.3 Chemical Name: N-[3-[5-(2-amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluoro-benzenesulfonamide

Activity: EP2 receptor antagonist . Function/Pharmacology: Potent and selective prostaglandin EP2 receptor antagonist, KB = 2.4 and 34.5 nM for EP2 and DP1 receptors respectively. Displays >500-fold selectivity for EP2 over other prostanoid receptors.1 Inhibits butaprost-induced proinflammatory cytokine production, cell proliferation and invasion of PC-3 cells in vitro.2 Inhibits PGE2-induced inflammatory response and may represent a novel pharmacologic intervention for tumorigenesis resulting from inflammation.1 Chemical Name: (2E)-N-[2-(2-Methyl-1H-indol-1-yl)ethyl]-3-(3,4,5-trimethoxyphenyl)-2-propenamide

Activity: Cytotoxic activity . Function/Pharmacology: Represents a novel class of ansamycins.1 Inhibits osteoclastic bone resorption.2 Potentiates the activity of several clinically useful antitumor agents.3 Translation inhibitor which prevents ICAM-1 expression induced by pro-inflammatory cytokines.4 Chemical Name: Fermentation product from Streptomyces sp

Activity: Geldanamycin affinity chromatography ligand . Function/Pharmacology: Semi-synthetic analog of geldanamycin containing a linker bearing a free NH2 functional group for conjugation. Selectively binds to HSP90 and may be used to prepare geldanamycin beads and affinity columns for purification of HSP90 and associated client proteins.1,2 Has been used in a copolymeric composition for geldanamycin sustained delivery and controlled release3,4 as well as other applications. Chemical Name: 17-(6-Aminohexylamino)-17-demethoxygeldanamycin

Activity: IRE1 ribonuclease inhibitor . Function/Pharmacology: Selective inhibitor of IRE1α ribonuclease (RNase) activity (IC50 = 60 nM). Covalently binds to lysine 907 in the IRE1 endonuclease domain, blocking substrate access to the active site of IRE1α and inactivating both XBP1 splicing and IRE1α-mediated mRNA degradation but not IRE1 kinase activity1. Inhibits IRE1α in response to hypoxia or other ER stress-inducing agents but has no effect on proliferation or clonogenic survival of hypoxic cells2. Blocks production of IL-4, IL-5 and IL-13 production in T cells3. Prevents the splicing of the XBP1 mRNA in response to ER stress caused by mutant proinsulin production in pancreatic β-cells4. Chemical Name: 7-Hydroxy-4-methyl-2-oxo-2H-1-benzopyran-8-carboxaldehyde

Activity: Mitochondria specific, photo-activated protonophore . Function/Pharmacology: Mitochondria-targeted, photo-activated protonophore.1 This novel tool consists of three structural units, a caged protonophore, a photocleavable linker coupled to a triphenylphosphonium moiety which confers selective uptake by the mitochondria.2 Cells are treated with Mito-Photo-DNP at 200 nM and irradiated with UV light at 355 nm. Mito-Photo-DNP can be employed for selective uncoupling of either individual or a small number of mitochondria within a cell when used with fluorescence imaging.1,3 Chemical Name: (4-(3-((2,4-Dinitrophenoxy)methyl)-4-nitrophenoxy)butyl)triphenylphosphonium

Activity: Soluble guanylyl cyclase activator . Function/Pharmacology: Nitric oxide-independent activator of soluble guanylyl cyclase (sGC). Significantly elevates cGMP levels and inhibits collagen-stimulated aggregation of rabbit platelets (IC50 = 14.6 μM).1 Induces human endometrial cancer cell senescence via modulation of HIF1 activity.2 Induces degradation of HIF13 Protects against glutamate-induced neuronal damage4 and -amyloid-induced toxicity in differentiated PC12 cells5. Chemical Name: 3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole

Activity: U-73122 negative control . Function/Pharmacology: Negative control for phospholipase C inhibitor U-731221,2. Elicits unexpected effects on rabbit parietal cells3. Cell permeable. Chemical Name: 1-[6-[[(17β)-3-Methoxyestra-1,3,5(10)-trien-17-yl]ammonia]hexyl]-pyrrolidine-2,5-dione