TMI-1  (Synonyms: WAY-171318)

TMI-1 (WAY-171318) inhibits TNF converting enzyme (TACE) (IC₅₀ of 8.4 nM), ADAM-TS-4, ADAM-17 and various MMPs with oral activity. TMI-1 significantly suppresses the secretion of TNF-α , alleviating collagen-induced arthritis in mice. TMI-1 inhibits cancer cell proliferation, induces apoptosis through a caspase-dependent pathway. TMI-1 also reverses TRPV1 upregulation and lowers the levels of inflammatory factors (TNF-α、IL-1β、IL-6) in nerve cells, protecting against paclitaxel-induced neurotoxicity. TMI-1 leads to changes in pro-atherogenic lipoprotein profiles, but does not affect the progression of early lesions^[1][2][3][4].

TMI-1 inhibits TNF-α secretion in mouse monocyte Raw cells with an IC₅₀ of 40 nM, in human monocyte THP-1 cells with an IC₅₀ of 200 nM, in primary human monocyte lines with an IC₅₀ of 190 nM, and in human whole blood with an IC₅₀ of 300 nM^[1].
TMI-1 inhibits the shedding of TNFR II in human whole blood, with an IC₅₀ of 0.72μM^[1].
TMI-1 (0-20 μM, 5 days) shows a dose-dependent inhibition of proliferation in breast cancer cell lines BT-20, SUM149, MDA-MB-231, SK-BR-3, L226, SUM190, T147D and Cama-1, with ED₅₀ of 1.3, 1.5, 8.1, 1.6, 2.0, 2.0, 2.5, and 2.5 μM respectively, and induces the activity of Caspase-3 and Caspase-7 without affecting the vitality of normal cells^[2].
TMI-1 (0-20 μM, 48 h) inhibits the cell cycle of breast cancer cells SUM149, promotes apoptosis, activates Caspase-3, Caspase-7, Caspase-8, Caspase-9, and increases ROS production^[2].
TMI-1 (4 ng/mL, 24 h) improves the degenerative changes in the axons of 50B11 cells induced by paclitaxel (HY-B0015) and enhances the growth of neurites induced by forskolin (HY-15371), and this effect is dose-dependent^[3].
TMI-1 (0.04-4 ng/mL, 24 h) reduces the expression of TRPV1 protein in 50B11 cells in a dose-dependent manner, along with a decrease in the expressions of PKC, PI3K, NF-κB, TNF-α, IL-1β, and IL-6 mRNA, as well as calcium influx^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TMI-1 (0-50 mg/kg, twice a day, 14-17 days, oral) is effective in both therapeutic and preventive arthritis mouse models, reducing disease severity^[1].
TMI-1 (100 mg/kg, daily, 30 days, oral) slows down breast cancer tumor growth and prevents tumor occurrence in a breast cancer mouse model^[2].
TMI-1 (100 mg/kg, daily, 4 weeks, oral) alters the lipoprotein profile that promotes atherosclerosis but does not affect the progression of early atherosclerotic lesions^[4].
Analysis of pharmacokinetics in Balb/CJ mice after a single oral dose of 50 mg/kg^[1]

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

398.50

C₁₇H₂₂N₂O₅S₂

287403-39-8

Solid

White to off-white

O=C([C@@H]1N(S(=O)(C2=CC=C(OCC#CC)C=C2)=O)CCSC1(C)C)NO

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Zhang Y, et al. Identification and characterization of 4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl-(3S)thiomorpholinecarboxamide (TMI-1), a novel dual tumor necrosis factor-alpha-converting enzyme/matrix metalloprotease inhibitor for the treatment of rheumatoid arthritis. J Pharmacol Exp Ther. 2004 Apr;309(1):348-55.  [Content Brief]

  [2]. Mezil L, et al. Tumor selective cytotoxic action of a thiomorpholin hydroxamate inhibitor (TMI-1) in breast cancer. PLoS One. 2012;7(9):e43409.  [Content Brief]

  [3]. Yesul Kim, et al. TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro. Front Pharmacol. 2022 Feb 16:13:842779.  [Content Brief]

  [4]. Wynand Melenhorst, et al. ADAM17 INHIBITION IN APOE DEFICIENT MICE RESULTS IN A PROATHEROGENIC LIPOPROTEIN PROFILE WITHOUT AFFECTING ATHEROSCLEROSIS. University of Groningen.