General Information of Drug (ID: DMWD39E)

Drug Name
Tr-14035
Synonyms
232271-19-1; TR-14035; (S)-2-(2,6-Dichlorobenzamido)-3-(2',6'-dimethoxy-[1,1'-biphenyl]-4-yl)propanoic acid; CHEMBL91485; N-(2,6-DICHLOROBENZOYL)-4-(2,6-DIMETHOXYPHENYL)-L-PHENYLALANINE; C24H21Cl2NO5; DRSJLVGDSNWQBI-SFHVURJKSA-N; TR 14035; SCHEMBL1222491; BDBM16801; CTK8C1530; MolPort-023-334-229; ZINC1490484; ANW-66841; N-Acyl-4-arylphenylalanine analogue.; AKOS016008162; CS-1812; CS-W000631; MP-2027; NCGC00390619-01; SB683698; HY-15770; AK-95353; AJ-26339; KB-210922; TC-155586; AB0077984; AX8237663; ST24020804; Z4458
Indication
Disease Entry ICD 11 Status REF
Multiple sclerosis 8A40 Discontinued in Phase 1 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 474.3
Topological Polar Surface Area (xlogp) 5.6
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C24H21Cl2NO5
IUPAC Name
(2S)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid
Canonical 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
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
InChIKey
DRSJLVGDSNWQBI-SFHVURJKSA-N
Cross-matching ID
PubChem CID
9912743
CAS Number
232271-19-1
TTD ID
D02WII
VARIDT ID
DR01351

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Integrin alpha-4/beta-1 (ITGA4/B1) TT6S84X ITA4_HUMAN-ITB1_HUMAN Modulator [2]
Integrin alpha-4/beta-7 (ITGA4/B7) TT7ZMI1 ITA4_HUMAN-ITB7_HUMAN Modulator [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [3]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 08 Disease of the nervous system
Disease Class ICD-11: 8A40 Multiple sclerosis
The Studied Tissue Plasmacytoid dendritic cells
The Studied Disease Multiple sclerosis [ICD-11:8A40]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTP OATP1A2 6.43E-01 -3.17E-02 -2.27E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 3.23E-01 6.36E-02 5.84E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012563)
2 Pharmacokinetics and metabolism of TR-14035, a novel antagonist of a4ss1/a4ss7 integrin mediated cell adhesion, in rat and dog. Xenobiotica. 2005 Apr;35(4):373-89.
3 Characterization of hepatobiliary transport systems of a novel alpha4beta1/alpha4beta7 dual antagonist, TR-14035. Pharm Res. 2006 Nov;23(11):2646-56.
4 Cellular entry of thyroid hormones by organic anion transporting polypeptides. Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):209-21.
5 Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
6 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
7 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
8 Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
9 The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
10 Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
11 Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
12 FDA Drug Development and Drug Interactions
13 Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
14 Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95.
15 Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
16 Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53.
17 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
18 Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
19 Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Mol Pharm. 2004 Jan 12;1(1):49-56.
20 Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Drug Metab Dispos. 2000 Jul;28(7):801-6.
21 Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82.
22 Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
23 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
24 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
25 Vedolizumab: an 47 integrin inhibitor for inflammatory bowel diseases.Ann Pharmacother.2014 Dec;48(12):1629-35.
26 Oral treatment with a novel small molecule alpha 4 integrin antagonist, AJM300, prevents the development of experimental colitis in mice. J Crohns Colitis. 2013 Dec;7(11):e533-42.
27 Integrins as therapeutic targets: lessons and opportunities. Nat Rev Drug Discov. 2010 Oct;9(10):804-20.
28 Pharmacodynamic consequences of administration of VLA-4 antagonist CDP323 to multiple sclerosis subjects: a randomized, double-blind phase 1/2 study.PLoS One.2013;8(3):e58438.
29 Firategrast for relapsing remitting multiple sclerosis: a phase 2, randomised, double-blind, placebo-controlled trial.Lancet Neurol.2012 Feb;11(2):131-9.
30 Pharmacoscintigraphic comparison of HMR 1031, a VLA-4 antagonist, in healthy volunteers following delivery via a nebulizer and a dry powder inhaler. Am J Ther. 2004 Mar-Apr;11(2):103-13.
31 US patent application no. 2010,0278,784, Methods and compositions for treating skin conditions.
32 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2580).