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

General Information of Drug (ID: DMI5OXG)

• Drug Name: Latanoprost Drug Info
• Synonyms: Catioprost; Xalatan; Latanoprost free acid; L1167_SIGMA; PhXA41; XA41; AR-202; Nova-21027; PHXA-41; XA-41; Xalatan (TN); Latanoprost (JAN/USAN/INN); PhXA34 [as 15(R,S)-isomer]; Isopropyl (5Z,9alpha,11alpha,15R)-9,11,15-trihydroxy-17-phenyl-18,19,20-trinorprost-5-en-1-oate; Isopropyl (5Z,9alpha,11alpha,15R)-9,11,15-trihydroxy-17-phenyl-18,19,20-trinor-prost-5-en-1-oate; Isopropyl (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((3R)-3-hydroxy-5-phenylpentyl)cyclopentyl)-5-heptenoate; Propan-2-yl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate; Propan-2-yl (5Z)-7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl}hept-5-enoate

Indication

Disease Entry	ICD 11	Status	REF
Ocular hypertension	9C61.01	Approved	[1]
Open-angle glaucoma	9C61	Approved	[2]
OPTN-related open angle glaucoma		Approved	[1]
Glaucoma/ocular hypertension	9C61	Phase 2	[3]
Ocular disease	1F00.1Z	Investigative	[4]

• Therapeutic Class: Antihypertensive Agents
• Cross-matching ID:
  PubChem CID: 5311221
  ChEBI ID: CHEBI:6384
  CAS Number: CAS 130209-82-4
  TTD Drug ID: DMI5OXG
  VARIDT Drug ID: DR00168
  ACDINA Drug ID: D01199

Molecule-Related Drug Atlas

Drug(s) Targeting Prostaglandin F2-alpha receptor (PTGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[8]
BOL-303259-X	DM2EXC5	Open-angle glaucoma	9C61	Approved	[9]
Tafluprost	DMFC41K	Glaucoma/ocular hypertension	9C61	Approved	[10]
Carboprost Tromethamine	DMS3508	Abortion	JA00	Approved	[11]
Travoprost	DM20K91	Ocular hypertension	9C61.01	Approved	[12]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[13]
PGF2ALPHA-IE	DM5DAP3	Glaucoma/ocular hypertension	9C61	Phase 3	[14]
ONO-9054	DM5O6GC	Glaucoma/ocular hypertension	9C61	Phase 2	[15]
PDC-41	DM74YO8	Dysmenorrhea	GA34.3	Phase 1	[16]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[17]

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	[18]
L-Glutamic Acid	DM4PUDW	Schizophrenia	6A20	Approved	[19]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[22]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[23]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[24]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[25]
Digoxin	DMQCTIH	Arrhythmia	BC9Z	Approved	[26]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[27]

Drug(s) Transported By Organic anion transporting polypeptide 2A1 (SLCO2A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[18]
Alprostadil	DMWH7NQ	Aorta coarctation		Approved	[28]
Iloprost	DMVPZBE	Pulmonary arterial hypertension	BB01.0	Approved	[28]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[28]

Drug(s) Affected By Bile salt export pump (ABCB11)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[29]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[30]
Glipizide	DMZA5PQ	Diabetic complication	5A2Y	Approved	[30]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[31]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[29]
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[30]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[32]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[29]
Drospirenone	DM1A9W3	Acne vulgaris	ED80	Approved	[7]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin F2-alpha receptor (PTGFR)	TTT2ZAR	PF2R_HUMAN	Agonist	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 2A1 (SLCO2A1)	DT021JD	SO2A1_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[7]

References

• [1] Latanoprost FDA Label
• [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: 1961).
• [3] Clinical pipeline report, company report or official report of Mati therapeutics.
• [4] 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: 344).
• [5] PGF(2alpha) FP receptor contributes to brain damage following transient focal brain ischemia. Neurotox Res. 2009 Jan;15(1):62-70.
• [6] The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol Vis Sci. 2010 May;51(5):2504-11.
• [7] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [8] Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.Expert Opin Ther Pat. 2015 Jul;25(7):837-44.
• [9] Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2alpha agonist, in preclinical models. Exp Eye Res. 2011 Sep;93(3):250-5.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8.
• [13] Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.
• [14] Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Exp Eye Res. 1994 Oct;59(4):401-7.
• [15] IOP-Lowering Effect of ONO-9054, A Novel Dual Agonist of Prostanoid EP3 and FP Receptors, in Monkeys. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2547-52.
• [16] THG113: a novel selective FP antagonist that delays preterm labor. Semin Perinatol. 2002 Dec;26(6):389-97.
• [17] Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor. Biochem J. 2003 Apr 15;371(Pt 2):443-9.
• [18] 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.
• [19] The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.60.1.20)
• [20] 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.
• [21] 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.
• [22] Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
• [23] Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
• [24] pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
• [25] Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36.
• [26] Drug Interactions in Infectious Diseases.
• [27] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
• [28] Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9.
• [29] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [30] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [31] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [32] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.