TM5441

SKU: orb1303019

Description

TM5441 is an orally active small molecule inhibitor of fibrinogen activator inhibitor-1 (PAI-1). It exhibits cytotoxic activity against various human cancer cell lines in vitro and has shown efficacy in preclinical models of hypertension and vascular aging. This compound is a research tool for studying oncology, cardiovascular disease, and senescence.

Research Area

Cell Biology, Metabolism Research

Key Properties

• CAS Number: 1190221-43-2
• MW: 428.82
• Purity: 98.87%
• Formula: C₂₁H₁₇ClN₂O₆
• SMILES: OC(=O)c1cc(Cl)ccc1NC(=O)COCC(=O)Nc1cccc(c1)-c1ccoc1
• Target: Apoptosis,PAI-1
• Solubility: DMSO:5.67 mg/mL (13.22 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.33 mM)

Bioactivity

• Target IC50:
  Tumor cells:9.7～60.3 μM
• In Vivo:
  METHODS: High-fat diet (HFD)-fed C57BL/6J mice were treated with 20 mg/kg of TM5441 daily to study the effect of TM5441, an oral PAI-1 inhibitor that lacks bleeding risk, on HFD-induced NAFLD. RESULTS Early and delayed treatment with TM5441 reduced hepatic steatosis, and both strategies abolished hepatic insulin resistance and mitochondrial dysfunction, manifested by enhanced p-Akt and p-GSK3β, reduced p-JNK signaling, and p-AMPK and PGC-1α activation.
• In Vitro:
  METHODS: TM5441 (1-100μM) was used to further study the survival of HT1080, HCT116, Daoy, MDA-MB-231 and Jurkat. RESULTS Cell viability treated with TM5441 significantly decreased in a dose-dependent manner by 50%, ranging between 13.9 and 51.1μM. METHODS: Cultures of human endothelial cells EA.hy926 were pretreated with TM5441 (10 μM) for 24 h and then treated with doxorubicin (Dox) in triplicate for 4 days. Total protein and RNA were collected from three independently treated wells and combined to explore the protective effect of TM5441 on Dox-induced cellular senescence. RESULTS TM5441 treatment inhibited Dox-induced expression levels of p53, PAI-1, p16, p21 and IGFBP3 in human endothelial cells.
• Animal Research:
  TM5441 is prepared in 0.5% carboxymethyl cellulose.Mice: TM5275 at 50 mg/kg/day and TM5441 at 10 mg/kg/day were orally administered in control and diabetic mice for 16 weeks. Mice were monitored at least once a day. At the end, blood is collected for measurement of plasma glucose and creatinine, urine for protein measurement, and kidneys for immunohistochemical analysis.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Plasminogen activator inhibitor-1, TM5441, TM-5441, TM 5441, inhibit, Inhibitor, PAI-1, PAI1, Apoptosis

Compound Identifiers

PubChem CID

44250349