TMI-1

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].

Product Specifications

CAS Number

[287403-39-8]

Product Name Alternative

WAY-171318

UNSPSC

12352005

Target

Apoptosis; Caspase; Interleukin Related; MMP; TNF Receptor

Type

Reference compound

Related Pathways

Apoptosis; Immunology/Inflammation; Metabolic Enzyme/Protease

Applications

COVID-19-immunoregulation

Field of Research

Cancer; Infection; Inflammation/Immunology; Neurological Disease

Assay Protocol

https://www.medchemexpress.com/tmi-1.html

Purity

99.57

Solubility

DMSO : ≥ 100 mg/mL

Smiles

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

Molecular Formula

C17H22N2O5S2

Molecular Weight

398.50

References & Citations

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