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

General Information of Drug (ID: DM4WVC5)

• Drug Name: lifitegrast Drug Info
• Synonyms: Lifitegrast; Xiidra; 1025967-78-5; SAR-1118; SAR 1118; UNII-038E5L962W; CHEMBL2048028; 038E5L962W; (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid; (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid;(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid; SAR-1118; SAR-1119; SHP606; SPD606

Indication

Disease Entry	ICD 11	Status	REF
Dry eye disease	9E1Z	Approved	[1]
Allergic conjunctivitis	9A60.02	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 11965427
  ChEBI ID: CHEBI:133023
  CAS Number: CAS 1025967-78-5
  TTD Drug ID: DM4WVC5
  VARIDT Drug ID: DR00072
  ACDINA Drug ID: D01208

Molecule-Related Drug Atlas

Drug(s) Targeting Intercellular adhesion molecule ICAM-1 (ICAM1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alicaforsen	DMQ509J	Lleum inflammation	1A40.0	Phase 3	[6]
BI-505	DMSZQHX	Multiple myeloma	2A83	Phase 2	[7]
APC-8015F	DM3VP19	Prostate cancer	2C82.0	Phase 2	[8]
AIC100	DMSPBOW	Thyroid cancer	2D10	Phase 1	[9]
GI-270384X	DM3KN2Q	Inflammatory bowel disease	DD72	Terminated	[10]
A-252444.0	DMDTA36	Inflammation	1A00-CA43.1	Terminated	[11]
MOR-102	DMRCH1M	Psoriasis vulgaris	EA90	Terminated	[12]
ISIS-1939	DMGN4OQ	Discovery agent	N.A.	Investigative	[13]

Drug(s) Targeting Integrin alpha-L (ITGAL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Efalizumab	DMCKL5V	Psoriasis vulgaris	EA90	Approved	[14]
BMS-587101	DMS2IC9	Psoriasis vulgaris	EA90	Discontinued in Phase 2	[15]
IC-747	DM1LVRP	Psoriasis vulgaris	EA90	Discontinued in Phase 2	[16]
Cytolin	DMV8APG	Human immunodeficiency virus infection	1C62	Preclinical	[17]
A-286982	DM98VFW	Discovery agent	N.A.	Investigative	[18]
Leukotoxin	DMYX2NJ	Autoimmune diabetes	5A10	Investigative	[19]
LFA703	DM5G307	Discovery agent	N.A.	Investigative	[20]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[21]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[24]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[25]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[26]
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[27]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[28]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[29]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[30]

Drug(s) Transported By Organic anion transporting polypeptide 2B1 (SLCO2B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[31]
L-Glutamic Acid	DM4PUDW	Schizophrenia	6A20	Approved	[32]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[33]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[34]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[35]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[36]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[37]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[38]
Digoxin	DMQCTIH	Arrhythmia	BC9Z	Approved	[39]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[40]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Integrin alpha-L (ITGAL)	TT48WR6	ITAL_HUMAN	Modulator	[3]
Intercellular adhesion molecule ICAM-1 (ICAM1)	TTCT6F7	ICAM1_HUMAN	Inhibitor	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[5]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[5]

References

• [1] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [2] 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. (Ligand id: 7533).
• [3] Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118). J Ocul Pharmacol Ther. 2013 May;29(4):395-402.
• [4] Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye. ACS Med Chem Lett. 2012 Jan 31;3(3):203-6.
• [5] Clinical Pharmacology and Biopharmaceutics review(s)
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer Cell. 2013 Apr 15;23(4):502-15.
• [8] National Cancer Institute Drug Dictionary (drug id 561410).
• [9] Clinical pipeline report, company report or official report of AffyImmune Therapeutics.
• [10] Inhibition of endothelial cell adhesion molecule expression improves colonic hyperalgaesia. Neurogastroenterol Motil. 2009 Feb;21(2):189-96.
• [11] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012566)
• [12] Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model. Br J Dermatol. 2005 Oct;153(4):758-66.
• [13] Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J Biol Chem. 1991 Sep 25;266(27):18162-71.
• [14] [Successful therapy of discoid lupus erythematosus with efalizumab]. Hautarzt. 2010 Mar;61(3):246-9.
• [15] Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): structure-activity relationships leading to the identification of 6-(... J Med Chem. 2010 May 13;53(9):3814-30.
• [16] HECA-452+ T Cells Migrate Through Superficial Vascular Plexus but Not Through Deep Vascular Plexus Endothelium. Journal of Investigative Dermatology. 04/1997; 108(3):343-8.
• [17] Cytokine-induced phagocyte adhesion to human mesangial cells: role of CD11/CD18 integrins and ICAM-1. Am J Physiol. 1991 Dec;261(6 Pt 2):F1071-9.
• [18] Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5269-73.
• [19] 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: 2451).
• [20] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [21] Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
• [22] 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.
• [23] Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
• [24] 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.
• [25] Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
• [26] Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
• [27] 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.
• [28] 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.
• [29] Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82.
• [30] Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
• [31] Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60.
• [32] The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.60.1.20)
• [33] Small-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP. J Pharm Sci. 2017 Sep;106(9):2688-2694.
• [34] 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.
• [35] Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
• [36] Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
• [37] pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
• [38] Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36.
• [39] Drug Interactions in Infectious Diseases.
• [40] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.