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

General Information of Drug (ID: DM2EXC5)

• Drug Name: BOL-303259-X Drug Info
• Synonyms: Latanoprostene bunod; Latanoprostene bunod); NCX-116; PF-03187207; PF-3187207; BOL-303259-X1; NO donors (glaucoma), NicOx/Pfizer; NO-donating prostaglandin F2-alpha analogs (glaucoma), Pfizer; NO-donating prostaglandin F2-alpha analogs (glaucoma), NicOx/Pfizer; Nitric oxide-donating prostaglandin F2-alpha analogs (eye disease), NicOx/Pfizer; NO-donating prostaglandin F2-alpha analogs (glaucoma), NicOx/ Bausch & Lomb

Indication

Disease Entry	ICD 11	Status	REF
Open-angle glaucoma	9C61	Approved	[1]
Renal cell carcinoma	2C90	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 11156438
  CAS Number: CAS 860005-21-6
  TTD Drug ID: DM2EXC5
  VARIDT Drug ID: DR00093
  ACDINA Drug ID: D01200

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	[5]
Latanoprost	DMI5OXG	Ocular hypertension	9C61.01	Approved	[6]
Tafluprost	DMFC41K	Glaucoma/ocular hypertension	9C61	Approved	[7]
Carboprost Tromethamine	DMS3508	Abortion	JA00	Approved	[8]
Travoprost	DM20K91	Ocular hypertension	9C61.01	Approved	[9]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[10]
PGF2ALPHA-IE	DM5DAP3	Glaucoma/ocular hypertension	9C61	Phase 3	[11]
ONO-9054	DM5O6GC	Glaucoma/ocular hypertension	9C61	Phase 2	[12]
PDC-41	DM74YO8	Dysmenorrhea	GA34.3	Phase 1	[13]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[14]

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	[15]
L-Glutamic Acid	DM4PUDW	Schizophrenia	6A20	Approved	[16]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[19]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[20]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[21]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[22]
Digoxin	DMQCTIH	Arrhythmia	BC9Z	Approved	[23]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[24]

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	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[4]

References

• [1] Evaluation of the Effect of Latanoprostene Bunod Ophthalmic Solution, 0.024% in Lowering Intraocular Pressure over 24 in Healthy Japanese Subjects.Adv Ther. 2015 Nov;32(11):1128-39.
• [2] ClinicalTrials.gov (NCT01895972) A Study Evaluating the Long-Term Safety of Latanoprostene Bunod Ophthalmic Solution 0.024%, in Japanese Subjects With Open-Angle Glaucoma or Ocular Hypertension. U.S.National Institutes of Health.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] PGF(2alpha) FP receptor contributes to brain damage following transient focal brain ischemia. Neurotox Res. 2009 Jan;15(1):62-70.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8.
• [10] 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.
• [11] Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Exp Eye Res. 1994 Oct;59(4):401-7.
• [12] 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.
• [13] THG113: a novel selective FP antagonist that delays preterm labor. Semin Perinatol. 2002 Dec;26(6):389-97.
• [14] 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.
• [15] 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.
• [16] The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.60.1.20)
• [17] 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.
• [18] 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.
• [19] Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
• [20] Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
• [21] pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
• [22] Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36.
• [23] Drug Interactions in Infectious Diseases.
• [24] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.