| Identification | Back Directory | [Name]
TMI 1 | [CAS]
287403-39-8 | [Synonyms]
TMI 1
TMI 1,TMI1
TMI-1 >=98% (HPLC)
(3S)-4-[[4-(2-Butyn-1-yloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl-3-thiomorpholinecarboxamide
3-Thiomorpholinecarboxamide, 4-[[4-(2-butyn-1-yloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl-, (3S)- | [Molecular Formula]
C17H22N2O5S2 | [MDL Number]
MFCD09027399 | [MOL File]
287403-39-8.mol | [Molecular Weight]
398.5 |
| Chemical Properties | Back Directory | [density ]
1.325±0.06 g/cm3(Predicted) | [storage temp. ]
room temp | [solubility ]
DMSO: 25 mg/ml | [form ]
powder | [pka]
9.25±0.23(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Description]
TMI 1 is an inhibitor of disintegrin and metalloproteinase domain-containing protein 17 (ADAM17/TACE; IC50 = 8.4 nM in a cell-free enzyme assay). It inhibits matrix metalloproteinase-1 (MMP-1), -2, -7, -9, -13, and -14, as well as ADAM-TS-4 in vitro (IC50s = 6.6, 4.7, 26, 12, 3, 26, and 100 nM, respectively). It also inhibits ADAM8, -10, -12, and -17/TACE in cell-free enzyme assays with Ki values of 21, 16, 1.8, and 0.079 nM, respectively, with slow-binding inhibition of ADAM17/TACE but not the other ADAM enzymes. TMI 1 inhibits LPS-induced TNF-α secretion in Raw and THP-1 cells (IC50s = 40 and 200 nM, respectively), as well as in isolated human monocytes and whole blood (IC50s = 190 and 300 nM, respectively). It inhibits the production of TNF-α ex vivo in synovium isolated from the inflamed joints of patients with rheumatoid arthritis with IC50 values of less than 100 nM without inhibiting TNF-α expression in vitro. TMI 1 inhibits LPS-induced TNF-α production in mice (ED50 = 5 mg/kg) and reduces disease severity in mouse models of collagen-induced arthritis. It also decreases cell viability of (ED50s = 1.3-8.1 μM), and induces caspase-3/7 activity in, a variety of cancer cell lines and induces tumor apoptosis and reduces tumor growth in an MMTV-ErbB2/neu mouse model of breast cancer when administered at a dose of 100 mg/kg. | [Uses]
TMI 1 is a dual TACE/MMP inhibitor, which represents a unique class of orally bioavailable small molecule TNF inhibitors that may be effective and beneficial for treating rhuematoid arthritis. | [storage]
Store at -20°C | [References]
[1] YUHUA ZHANG. 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]. Journal of Pharmacology and Experimental Therapeutics, 2004, 309 1: 348-355. DOI: 10.1124/jpet.103.059675
[2] MARCIA L. MOSS Fred H R. Fluorescent substrates for the proteinases ADAM17, ADAM10, ADAM8, and ADAM12 useful for high-throughput inhibitor screening[J]. Analytical biochemistry, 2007, 366 2: Pages 144-148. DOI: 10.1016/j.ab.2007.04.043
[3] LYNDA MEZIL. Tumor selective cytotoxic action of a thiomorpholin hydroxamate inhibitor (TMI-1) in breast cancer.[J]. PLoS ONE, 2012: e43409. DOI: 10.1371/journal.pone.0043409 |
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| Company Name: |
Energy Chemical
|
| Tel: |
021-58432009 400-005-6266 |
| Website: |
http://www.energy-chemical.com |
| Company Name: |
Wuhan Topule
|
| Tel: |
+86-02787215551 +86-19945035818 |
| Website: |
http://www.topule.com/ |
|