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TR-14035

Catalog No. T5310 CAS 232271-19-1

Synonyms: MDK-1191

TR-14035 (MDK-1191) is a dual antagonist of α4β7/α4β1 integrins (IC50s: 7/87nM).

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TR-14035, CAS 232271-19-1

Pack Size	Availability	Price/USD
1 mg	In stock	$ 81.00
2 mg	In stock	$ 117.00
5 mg	In stock	$ 178.00
10 mg	In stock	$ 289.00
25 mg	In stock	$ 522.00
50 mg	In stock	$ 756.00
100 mg	In stock	$ 1,060.00
1 mL * 10 mM (in DMSO)	In stock	$ 189.00

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Purity: 99.81%

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Description	TR-14035 (MDK-1191) is a dual antagonist of α4β7/α4β1 integrins (IC50s: 7/87nM).
Targets&IC50	α4β7 integrin:7 nM, α4β1 integrin:87 nM
In vitro	TR-14035 (IC50: alpha(4)beta(7)/alpha(4)beta(1)=7/87 nM) has completed Phase I studies in Europe [1]. 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 [2]. 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 [3].
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 [2]. TR14035 blocked adhesion to HEVs (ED50: of 0.01-0.1 mpk i.v.) [3].
Cell Research	RPMI8866 cell line and Jurkat T lymphoblastoid cell line were grown as a suspension culture in RPMI 1640 media, 10% FCS, 2 mM glutamine, 100 units/mL penicillin G, 100 mg/mL streptomycin sulfate at 37 °C and 5% CO2. Adhesion assays have been detailed elsewhere. Microtiter plates were coated with 20 mg/mL HSA for 2 h at room temperature, washed once with PBS and derivatized with 10 mg/mL SPDP for 1 h. After washing, CS-1 (or sCS-1) derived peptide solution (100 mL at 100 μg/mL) was added to the wells and allowed to crosslink to the plates overnight at 4 °C. Non-reacted sites were blocked with 100 mL of 1% OV in PBS for 1 h at 37 °C. RPMI8866 cells were suspended in Dulbecco's modified Eagle's medium with 0.25% OV at a density of 2.5 ×106/mL and incubated for ~1 h at 37 °C with varying concentrations of antagonists on peptide-coated plates. Following washing (EL404 plate washer), bound cells were quantified by measuring endogenous N-acetyl-hexosaminidase activity by reading the optical density at 405 nm using the enzyme substrate p-nitrophenol-N-acetyl-b-d-glucoseaminide. IC50 values were generated by nonlinear regression from titration curves of antagonists from seven doses and reported as the average of a minimum of two experiments. Since experimental variability was noted with respect to the IC50 of the internal standard [(1S - cis) - N - [(3 - carboxy - 2,2,3 - trimethylcyclopentyl)- carbonyl]-O-[(2,6-dichlorophenyl)methyl]-l-tyrosine] a normalization procedure was done using the global mean value [IC50=0.224±0.17 μM (N=19)] of the internal standard. For the Jurkat cell adhesion assay, OV was replaced with 0.25% HSA for both blocking and adhesion buffers. Standard error of the mean for the Jurkat cell adhesion assay was typically <10% for each experiment and no normalization was needed [1].
Animal Research	For biliary excretion studies in mice and rats, a cannula (polyethylene tube, SP8 for mice and SP10 for rats) was inserted into the bile duct of the anesthetized animal. In the rat, after complete recovery from diethyl ether anesthesia, TR-14035 was administered intravenously at a dose of 3 mg/ml/kg, and the bile, urine, and blood were collected at designated time intervals. In the mouse, TR-14035 was administered intravenously at a dose of 3 mg/4 ml/kg, and the bile and blood were collected at designated time intervals under pentobarbital anesthesia. Blood was centrifuged to separate plasma, and all the samples were stored at j20 -C until analysis by LC-MSD [2].

Synonyms	MDK-1191
Molecular Weight	474.33
Formula	C24H21Cl2NO5
CAS No.	232271-19-1

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

H2O: Insoluble

DMSO: 40 mg/Ml (84.3 mM)

References and Literature

1. Sircar I, et al. Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: discovery of TR-14035, a dual alpha(4)beta(7)/alpha(4)beta(1) integrin antagonist. Bioorg Med Chem. 2002 Jun;10(6):2051-66. 2. Tsuda-Tsukimoto M, et al. Characterization of hepatobiliary transport systems of a novel alpha4beta1/alpha4beta7 dual antagonist, TR-14035. Pharm Res. 2006 Nov;23(11):2646-56. 3. Egger LA, et al. Alpha(4)beta(7)/alpha(4)beta(1) dual integrin antagonists block alpha(4)beta(7)-dependent adhesion under shear flow. J Pharmacol Exp Ther. 2002 Jul;302(1):153-62.

Related compound libraries

This product is contained In the following compound libraries：

Anti-Neurodegenerative Disease Compound Library Inhibitor Library Drug Repurposing Compound Library ReFRAME Related Library Bioactive Compound Library Bioactive Compounds Library Max Cytoskeletal Signaling Pathway Compound Library NO PAINS Compound Library Clinical Compound Library Orally Active Compound Library

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Keywords

TR-14035 232271-19-1 Cytoskeletal Signaling Integrin MDK1191 MDK-1191 autoimmune disease asthma inhibit MDK 1191 TR 14035 allergic TR14035 inflammation Inhibitor alpha(4) inhibitor

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