MLN7243

MLN7243 is an inhibitor of ubiquitin-activating enzyme (UAE, IC50 = 1 nM). It is selective for UAE over NEDD8-activating enzyme (NAE), SUMO-activating enzyme (SAE), and the autophagy-activating enzyme ATG7 (IC50s = 28, 850, and >10,000 nM, respectively). MLN7243 inhibits proliferation in a panel of 30 cancer cell lines (EC50s = 0.006-1.1 µM). It activates the unfolded protein response (UPR) and expansion of the endoplasmic reticulum surface area, a marker of ER stress, in HCT116 cells. In vivo, MLN7243 (12.5-25 mg/kg) reduces tumor growth in WSU-DLCL2, HCT116, Calu-6, THP-1, CWR22, HCC70, and MM.1S mouse xenograft models, as well as patient-derived xenograft (PDX) mouse models of colon, lung, breast, ovarian, and neck cancer.Formal Name: sulfamic acid, [(1R,2R,3S,4R)-2,3-dihydroxy-4-[[2-[3-[(trifluoromethyl)thio]phenyl]pyrazolo[1,5-a]pyrimidin-7-yl]amino]cyclopentyl]methyl ester. CAS Number: 1450833-55-2. Synonyms: TAK-243. Molecular Formula: C19H20F3N5O5S2. Formula Weight: 519.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 10 mg/ml, Methanol: 10 mg/ml. lambdamax: 217, 262, 309 nm. SMILES: FC(F)(F)SC1=CC(C2=NN3C(N=CC=C3N[C@H]4[C@H](O)[C@H](O)[C@@H](COS(N)(=O)=O)C4)=C2)=CC=C1. InChi Code: InChI=1S/C19H20F3N5O5S2/c20-19(21,22)33-12-3-1-2-10(6-12)13-8-16-24-5-4-15(27(16)26-13)25-14-7-11(17(28)18(14)29)9-32-34(23,30)31/h1-6,8,11,14,17-18,25,28-29H,7,9H2,(H2,23,30,31)/t11-,14-,17-,18+/m1/s1. InChi Key: KJDAGXLMHXUAGV-DGWLBADLSA-N.