Activators & Inhibitors

Activity: Exocytosis and endosomal recycling inhibitor . Function/Pharmacology: Endosidin-2 binds to the EXO70 subunit of the exocyst complex which results in inhibition of exocytosis and endosomal recycling in both plant and human cells and enhancement of plant vacuolar trafficking. EXO70 is a component of the octameric exocyst complex which tethers post-Golgi vesicles to the plasma membrane before SNARE- mediated membrane fusion2. Endosidin-2 was previously identified as a plant endomembrane trafficking disruptor3. It is a valuable new tool for the study of exocytosis. Chemical Name: (E)-3-Fluoro-N’-(4-hydroxy-3-iodo-5-methoxybenzylidene)benzohydrazide

Activity: BET Bromodomain inhibitor . Function/Pharmacology: Potent BET bromodomain inhibitor and is the active isomer. IC50 = 17.7, 32.6, 76.9 and 12942 nM respectively for BRD2 (N-terminal (N)), BRD4 (C-terminal (C)), BRD4 (N) and CREBBP respectively (data for + isomer).1 Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models.1 Induces squamous differentiation in NMC cell lines and inhibits tumor growth in NMC xenografts.2 Displays reversible contraceptive effects in male mice.3 Blocks inflammation and bone loss in periodontitis.4 Reverses CAR T cell extinction.5 Chemical Name: (6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid 1,1-dimethylethyl ester

Activity: PHGDH / serine biosynthesis inhibitor . Function/Pharmacology: Potent and selective inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), IC50=33 μM1. The action of PHGDH is the first committed step of serine biosynthesis2 and certain cancer cells overexpress PHGDH3. CBR-5884 inhibits serine biosynthesis in cells with no effect on two other dehydrogenases, lactate dehydrogenase and MDH1 and without general cytotoxic effects up to 40 μM. CBR-5884 is selectively toxic to tumor cells with high serine synthesis activity. A novel tool for selective inhibition of serine biosynthesis in cells which also provides further proof that PHGDH is a viable target for the development of novel anticancer agents1. Chemical Name: Ethyl 5-(furan-2-carboxamido)-3-methyl-4-thiocyanatothiophene-2-carboxylate

Activity: Matrix metalloprotease inhibitor (pan-spec.) . Function/Pharmacology: Potent, broad spectrum MMP inhibitor (IC50 =3, 4, 4, 6 and 20 nM for MMPs -1, -2, -9, -7 and -3 respectively). Exhibits antiproliferative, anti-invasive and antimetastatic activity in human colon1, ovarian2 and prostate3 xenografts in vivo. Attenuates neuroinflam-mation following focal cerebral ischemia in mice.4 Inhibits α-secretase.5 Inhibits snake venom (Bothrops asper) lethality.6 Chemical Name: (2R,3S)-N4-Hydroxy-N1-[(1S)-2-(methylamine)-2-oxo-1-(phenylmethyl)ethyl]-2-(2-methylpropyl)-3-[(2-thienylthio)methyl]butanediamide

Activity: Gq inhibitor . Function/Pharmacology: YM-254890 is a novel Gαq/11 inhibitor,1 U46619-induced platelet aggregation is inhibited but phorbol ester- or ionophore-induced aggregation is not2 (IC50 = 0.1-0.2 μM)1. It blocks Pasteurella multocida toxin-mediated activation of Gαq.3 A highly useful new tool for studying Gαq/11-coupled receptor signaling and resulting cellular events.4 Chemical Name: Cyclic depsipeptide from Chromobacterium sp.

Activity: Down regulates SnoN and Ski expression . Function/Pharmacology: Downregulates SnoN and Ski protein expression. Induces TGF-β signaling, independently of MAPK activation. Does not bind ribosomes or block protein synthesis. Chemical Name: 3’-[[(2S)-2-(Acetylamino)-3-(4-methoxyphenyl)-1-oxopropyl]amino]-3’-deoxy-N,N-dimethyladenosine

GBF1 inhibitor; induces Golgi disassembly

Activity: JARID1 lysine demethylase inhibitor . Function/Pharmacology: The JARID1 (Jumonji AT-Rich Interactive Domain 1) family of lysine demethylases demethylates the trimethylated lysine 27 in histone H3 (H3K4me3). PBIT is a potent and selective inhibitor of JARID1 (IC50 = 3, 4.9 and 6 μM for JARID1B, 1A and 1C, respectively). Selective for JARID1 over UTX and JMJD3. Treatment of cells with PBIT inhibits the demethylation of H3K4me3. It inhibits proliferation of breast cancer cell lines expressing high levels of JARID1B1. Chemical Name: 2-(4-Methylphenyl)-1,2-benzisothiazol-3(2H)-one

Activity: KDM5B histone demethylase inhibitor . Function/Pharmacology: AS-8351 has been used in a cocktail of nine small molecules used to efficiently induce cardiac reprogramming of human fibroblasts1. It is believed that AS-8351 exerts its effects by modulating the activity of the JmjC domain-containing histone demethylases (JmjC-KDM). Thus each of the 22 genes in the JmjC-KDM family was abrogated using small hairpin RNAs which showed that only knocking down KDM5B (or using another KDM5B inhibitor such as PBIT) could phenocopy AS-8351 in generating cardiomyocytes. This strongly suggests that KDM5B is the target of AS-8351.1 Chemical Name: 2-Hydroxy-1-naphthylaldehyde isonicotinolyhydrazone