TMI-005

TMI-005 is an inhibitor of disintegrin and metalloproteinase domain-containing protein 17/TNF-alpha converting enzyme (ADAM17/TACE), matrix metalloproteinase-1 (MMP-1), and MMP-13 (IC50s = 20, 33, and 8.1 nM, respectively). It inhibits LPS-induced TNF-alpha release in isolated human whole blood (IC50 = 144 ng/ml). TMI-005 (25 µM) reduces basal and ionizing radiation-induced secretion of the ADAM17/TACE substrates ALCAM and amphiregulin from A549 and NCI H125 cells. It inhibits proliferation of A549 cells when used at concentrations of 25 and 50 µM and sensitizes A549 and NCI H125 cells to ionizing radiation at 25 µM. TMI-005 (25 mg/kg twice per day) reduces tumor growth in an A549 mouse xenograft model when administered in combination with ionizing radiation.Formal Name: (3S)-N-hydroxy-4-[[4-[(4-hydroxy-2-butyn-1-yl)oxy]phenyl]sulfonyl]-2,2-dimethyl-3-thiomorpholinecarboxamide. CAS Number: 287405-51-0. Synonyms: Apratastat. Molecular Formula: C17H22N2O6S2. Formula Weight: 414.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMSO: 25 mg/ml, DMSO:PBS (pH 7.2) (1:40): 0.02 mg/ml, Ethanol: 10 mg/ml. lambdamax: 242 nm. SMILES: O=S(C1=CC=C(OCC#CCO)C=C1)(N2CCSC(C)(C)[C@@H]2C(NO)=O)=O. InChi Code: InChI=1S/C17H22N2O6S2/c1-17(2)15(16(21)18-22)19(9-12-26-17)27(23,24)14-7-5-13(6-8-14)25-11-4-3-10-20/h5-8,15,20,22H,9-12H2,1-2H3,(H,18,21)/t15-/m0/s1. InChi Key: MAVDNGWEBZTACC-HNNXBMFYSA-N.