TR-14035

SKU: orb1225574

Description

A potent, orally bioavailable, dual α4β7/α4β1 integrin antagonist with IC50 of 7/87 nM; blocks the binding of human α4β7 to an (125)I-MAdCAM-Ig fusion protein with IC50 of 0.75 nM; suppresses antigen-induced lung interleukin (IL)-5 mRNA upregulation, inhibits the leukocyte rolling flux, adhesion and emigration induced by IL4 in rats.Asthma Phase 1 Discontinued.

Key Properties

• CAS Number: 232271-19-1
• MW: 474.3333
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₁Cl₂NO₅
• SMILES: O=C(O)[C@H](CC1=CC=C(C2=C(OC)C=CC=C2OC)C=C1)NC(C3=C(Cl)C=CC=C3Cl)=O
• Target: Integrin
• Solubility: DMSO：≥ 41 mg/mL

Bioactivity

• In Vivo:
  Animal model: Male Brown Norway rats (250-300 g). Dosage: 3 mg/kg. Administration: Oral gavage, 1 h before and 3 h after antigen challenge. Result: Suppressed antigen-induced airway hyper-responsiveness and inflammation. Animal model: Male Sprague-Dawley rats (250-320 g). Dosage: 3 mg/ kg for i. v. ; 10 mg/kg for oral (Pharmacokinetic Analysis). Administration: Intravenous injection and oral administration. Result: Oral bioavailability (17.1%), Cmax (0.18 μg eq. /mL), T1/2 (0.28 h). Animal model: Male beagle dogs. Dosage: 3 mg/kg for i. v. ; 10 mg/kg for oral (Pharmacokinetic Analysis). Administration: Intravenous administration and oral administration. Result: Oral bioavailability (13.2%), Cmax (0.10 μg eq. /mL), T1/2 (0.81 h).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TR 14035 | TR14035

Quick Database Links

Gene Symbol

Integrin