Activators & Inhibitors

Activity: p97 AAA ATPase inhibitor . Function/Pharmacology: Potent and selective p97 AAA ATPase inhibitor, IC50=100 nM. Inhibits degradation of a p97-dependent but not p97-independent proteasome substrate in a dual-reporter cell line1. It impairs the endoplasmic reticulum-associated degradation (ERAD) pathway.1 ML241 and related inhibitors (DBeQ for example) have differential responses to p97 mutants as well as the presence of cofactors suggesting the possibility of context-dependent p97 inhibitors.2,3 Chemical Name: N-Benzyl-2-(2,3-dihydro-1,4-benzoxazin-4-yl)-5,6,7,8-tetrahydroquinazolin-4-amine

Activity: AhR modulator (SAhRM) . Function/Pharmacology: DiMNF is a selective aryl hydrocarbon receptor (AHR) modulator (SAhRM). It exhibits antiinflammatory activity including suppression of cytokine-mediated acute phase genes through dissociation of non-dioxin-response element (DRE) AHR activity from DRE-dependent xenobiotic gene expression1. Represses the cytokine-mediated induction of CD55 and therefore may have therapeutic potential in regulating the immune response to tumor formation2. Represses estrogen-inducible transcription3. Chemical Name: 2-(3,2-Dimethoxyphenyl)-4H-naphtho[1,2-b]pyran-4-one

Activity: Methyl-lysine binding protein inhibitor . Function/Pharmacology: The DNA damage response protein 53BP1 utilizes its tandem tudor domain to recognize dimethylated lysine 20 on histone (H4K20me2), a modification associated with double-strand DNA breaks. UNC-2170, identified by screening, was found to be a μM ligand for 53BP1 which also demonstrated at least 17-fold selectivity for 53BP1 over other methyl-lysine binding proteins. The compound functions as a 53BP1 antagonist in cell lysates and suppresses class switch recombination in whole cells, a process requiring a functioning 53BP1 tudor domain.1 Chemical Name: 3-Bromo-N-(3-(tert-butylamino)propyl)benzamide, hydrochloride

USP1 - UAF1 inhibitor

Activity: Estrogen-related receptor ERRβ and ERRγ agonist . Function/Pharmacology: Selective agonist at estrogen-related receptors ERR and ERR with minimal activity at ERR, ER and ER at concentrations up to 30 μM.1 Displays antiproliferative activity in prostate cancer cells.2 Promotes hormone production and cell fusion in cytotrophoblasts.3 In breast cancer cells DY131 arrests cells in G2/M and causes mitotic spindle defects.4 Inhibits osteoclastogenesis and protects against inflammatory bone loss induced by LPS in vivo.5 Chemical Name: N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine

Activity: PHLP phosphatase inhibitor / Laminin inhibitor . Function/Pharmacology: A potent inhibitor of the Leucine-rich repeat protein phosphatase (PHLPP) an enzyme which is a negative regulator of Akt and PKC (IC50=4 M).1 Increases AKT signaling in cells and prevents apoptosis. Also inhibits the 67 kDa laminin receptor (LR) interaction with laminin (LM) and selectively blocks LR-293 cell adhesion to LM IC50=19.35 M) impairing cell migration and invasion.2 Affects 37/67 kDa LR cell surface localization and interaction with cellular prion protein.3 Chemical Name: 1-((4-Methoxyanilino)methyl)-2-naphthol

Activity: PKC inhibitor . Function/Pharmacology: Selective, reversible, ATP-competitive inhibitor of protein kinase C. Inhibits PKCα, β1, β2, γ and ε, IC50= 8, 8, 14,13 and 39 nM respectively.1 Extremely useful tool for probing PKC-dependent physiology2 or signaling pathways3. Increases MSC adhesion to an ICAM-1 coated substrate in vitro and enables targeted delivery of systematically administered MSCs to inflamed sites in vivo in a CD11a-dependent manner.4 Cell permeable. Chemical Name: 3-[8-(Aminomethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methylindol-3-yl)pyrrol-2,5-dione hydrochloride

Activity: EPAC inhibitor . Function/Pharmacology: An allosteric inhibitor of Epac1, IC50= 4 μM.1 Does not inhibit PKA or adenylyl cyclase. Inhibits biological functions mediated by Epac including cAMP-induced increase in migration of cardiac fibroblasts. A useful tool for probing the role of Epac in cellular physiology and pathophysiology.2 Chemical Name: 5-((5-(2,4-Dichlorophenyl)furan-2-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione

Activity: CtBP inhibitor; cdc25 phosphatase inhibitor . Function/Pharmacology: A potent and selective inhibitor of Cdc25 phosphatase (Ki = 32, 96 and 40 nM for Cdc25A, B and C respectively). NSC-95397 inhibits the growth of several human tumor cell lines and blocks G2/M cell cycle transition.1 Induces cell cycle arrest, phosphorylation of EGFR and activation of ERK-1 and -2.2 Inhibits carboxyl-terminal binding protein a transcriptional corepressor that suppresses multiple pro-apoptotic and epithelial genes.3 Induces eryptosis in human erythrocytes.4 Chemical Name: 2,3-bis[(2-Hydroxyethyl)thiol]-1,4-naphthoquinone