TR-14035 (SB 683698, MDK-1191) is an alpha4beta (α4β) integrin dual acting antagonist. The IC50 values for alpha4beta7 (α4β7) and alpha4beta1 (α4β1) were 7 nM and 87 nM, respectively.

 

Brand: BCM

 

Target: Integrin

 

Signaling Pathways: Cytoskeletal Signaling

 

In Vitro: TR-14035 (IC50: alpha(4)beta(7)/alpha(4)beta(1)=7/87 nM) has completed Phase I studies in Europe. TR-14035 was taken up by rat and human hepatocytes by an apparently single saturable mechanism with K(m) of 6.7 and 2.1 microM, respectively, and taurocholate and digoxin reduced this uptake. OATP1B1/OATP-C and OATP1B3/OATP8 expressed in oocytes mediated the TR-14035 uptake with K(m) of 7.5 and 5.3 microM, respectively. TR14035 blocked the binding of human alpha(4)beta(7) to a (125)I-MAdCAM-Ig fusion protein with IC(50) values of 0.75 nM. Under shear flow in vitro, TR14035 blocked binding of human alpha(4)beta(7)-expressing RPMI-8866 cells or murine mesenteric lymph node lymphocytes to MAdCAM-Ig with IC(50) values of 0.1 microM.

 

In Vivo: Biliary excretion and total body clearance of unchanged TR-14035 in EHBRs were significantly lower than those in normal rats, while there was no difference in the clearances between wild and mdr1a/b- or Bcrp-knockout mice. TR14035 blocked adhesion to HEVs (ED50: of 0.01-0.1 mpk i.v.).

 

Boiling Point: 604.0±55.0 °C(Predicted)

 

pKa: 3.53±0.10(Predicted)

 

Solubility: Soluble in DMSO; soluble in Ethanol. Insoluble in Water.

 

Isomeric SMILES: COC1=C(C(=CC=C1)OC)C2=CC=C(C=C2)C[C@@H](C(=O)O)NC(=O)C3=C(C=CC=C3Cl)Cl  

 

InChIKey: DRSJLVGDSNWQBI-SFHVURJKSA-N  

 

InChI: InChI=1S/C24H21Cl2NO5/c1-31-19-7-4-8-20(32-2)21(19)15-11-9-14(10-12-15)13-18(24(29)30)27-23(28)22-16(25)5-3-6-17(22)26/h3-12,18H,13H2,1-2H3,(H,27,28)(H,29,30)/t18-/m0/s1

 

Attribute
[Chem Name]	(2S)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid
[Synonym]	TR-14035; SB 683698; MDK-1191
[CAS No.]	232271-19-1
[MDL No.]	MFCD09970400
[Formula]	C24H21Cl2NO5
[Molecular]	474.33
[Form]	Solid powder
[Storage]	Sealed in dry, 2-8°C

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