Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMWD39E)

• Drug Name: Tr-14035 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 9912743
  CAS Number: CAS 232271-19-1
  TTD Drug ID: DMWD39E
  VARIDT Drug ID: DR01351

Molecule-Related Drug Atlas

Drug(s) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[5]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[6]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[7]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[7]
Pravastatin	DM6A0X7	Hypercholesterolaemia	5C80.0	Approved	[9]
Mycophenolate mofetil	DMPQAGE	Organ transplant rejection	NE84	Approved	[10]
Atorvastatin	DMF28YC	Cardiovascular disease	BA00-BE2Z	Approved	[11]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[12]
Pitavastatin calcium	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[9]

Drug(s) Transported By Organic anion transporting polypeptide 1A2 (SLCO1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[13]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Atorvastatin	DMF28YC	Cardiovascular disease	BA00-BE2Z	Approved	[16]
Pitavastatin calcium	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[17]
Rosuvastatin	DMMIQ7G	Hypercholesterolaemia	5C80.0	Approved	[18]
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[19]
Enalapril	DMNFUZR	Hypertension	BA00-BA04	Approved	[20]
Cholic acid	DM7OKQV	Peroxisomal disorder	5C57	Approved	[21]
Liothyronine	DM6IR3P	Hypothyroidism	5A00	Approved	[22]

Drug(s) Targeting Integrin alpha-4/beta-7 (ITGA4/B7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN0002	DMP2LZ8	Crohn disease	DD70	Approved	[23]
TRK-170	DM13G5R	Inflammatory bowel disease	DD72	Phase 2	[24]
R1295	DMT8V9G	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[25]

Drug(s) Targeting Integrin alpha-4/beta-1 (ITGA4/B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AJM-300	DM5K6J4	Crohn disease	DD70	Phase 3	[26]
TRK-170	DM13G5R	Inflammatory bowel disease	DD72	Phase 2	[24]
R411	DMP7J0S	Asthma	CA23	Phase 2	[27]
CDP323	DMXYLTI	Multiple sclerosis	8A40	Phase 2	[28]
Firategrast	DMW2QYT	Multiple sclerosis	8A40	Phase 2	[29]
HMR-1031	DM695QT	Arthritis	FA20	Phase 1	[30]
CY-9652	DMPBCLA	Inflammation	1A00-CA43.1	Terminated	[31]
TCS2314	DMBVYQR	Discovery agent	N.A.	Investigative	[32]

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]

References

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• [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.
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• [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.
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• [12] FDA Drug Development and Drug Interactions
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• [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.
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• [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).