proTAME

proTAME is a cell-permeable prodrug form of N-4-tosyl-L-arginine methyl ester (TAME, Cay-17550), an inhibitor of the anaphase-promoting complex/cyclosome (APC/C), that is converted to TAME by intracellular esterases. proTAME (12 µM) blocks association of APC/C with the activator CDH1 and inhibits degradation of APC/C substrates in HeLa cells. It induces mitotic arrest in metaphase followed by cell death in synchronized HeLa H2B-GFP cells when used at a concentration of 12 µM. It also increases mitotic duration in asynchronous HeLa H2B-GFP cells at a concentration of 4 µM, an effect that is enhanced by knockdown of the APC/C co-activator CDC20. proTAME decreases the viability of several laboratory and primary patient-derived human multiple myeloma (MM) cell lines (IC50s = 2.8-20.3 µM) and increases apoptosis in RPMI-8226, LP-1, NCI-H929, and U266 MM cells when used at a concentration of 12 µM.Formal Name: (2S)-2-[[(4-methylphenyl)sulfonyl]amino]-9,13-dioxo-14-phenyl-7-[[[[(2-phenylacetyl)oxy]methoxy]carbonyl]amino]-10,12-dioxa-6,8-diazatetradec-6-enoic acid, methyl ester. CAS Number: 1362911-19-0. Synonyms: Pro-N-4-tosyl-L-arginine methyl ester. Molecular Formula: C34H38N4O12S. Formula Weight: 726.8. Purity: >90%. Formulation: (Request formulation change), A solution in methyl acetate. Solubility: DMSO: Soluble. SMILES: CC1=CC=C(S(N[C@H](C(OC)=O)CCC/N=C(NC(OCOC(CC2=CC=CC=C2)=O)=O)/NC(OCOC(CC3=CC=CC=C3)=O)=O)(=O)=O)C=C1. InChi Code: InChI=1S/C34H38N4O12S/c1-24-15-17-27(18-16-24)51(44,45)38-28(31(41)46-2)14-9-19-35-32(36-33(42)49-22-47-29(39)20-25-10-5-3-6-11-25)37-34(43)50-23-48-30(40)21-26-12-7-4-8-13-26/h3-8,10-13,15-18,28,38H,9,14,19-23H2,1-2H3,(H2,35,36,37,42,43)/t28-/m0/s1. InChi Key: MHYOVHULCQSDRZ-NDEPHWFRSA-N.