Details of the Drug

General Information of Drug (ID: DMALN2M)

• Drug Name: Cholyl lysyl fluorescein

Indication

Disease Entry	ICD 11	Status	REF
Hepatitis virus infection	1E50-1E51	Phase 2	[1]

• Chemical Identifiers:
  Formula: C51H63N3O11S
  IUPAC Name: 5-[[(5S)-5-carboxy-5-[[(4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]pentyl]carbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid
  Canonical SMILES: CC(CCC(=O)NC(CCCCNC(=S)NC1=CC(=C(C=C1)C2=C3C=CC(=O)C=C3OC4=C2C=CC(=C4)O)C(=O)O)C(=O)O)C5CCC6C5(C(CC7C6C(CC8C7(CCC(C8)O)C)O)O)C
  InChI: InChI=1S/C51H63N3O11S/c1-26(36-14-15-37-46-38(25-43(59)51(36,37)3)50(2)18-17-31(57)20-27(50)21-40(46)58)7-16-44(60)54-39(48(63)64)6-4-5-19-52-49(66)53-28-8-11-32(35(22-28)47(61)62)45-33-12-9-29(55)23-41(33)65-42-24-30(56)10-13-34(42)45/h8-13,22-24,26-27,31,36-40,43,46,55,57-59H,4-7,14-21,25H2,1-3H3,(H,54,60)(H,61,62)(H,63,64)(H2,52,53,66)/t26-,27+,31-,36-,37+,38+,39+,40-,43+,46+,50+,51-/m1/s1
  InChIKey: ZUJFMZPBQQCXQR-TZCNZRNCSA-N
• Cross-matching ID:
  PubChem CID: 44470395
  VARIDT ID: DR01616

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[2]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT00915057) Effect of Chronic Viral Hepatitis on the Pharmacokinetics of NRL972.
• [2] The emerging role of transport systems in liver function tests. Eur J Pharmacol. 2012 Jan 30;675(1-3):1-5.
• [3] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [4] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [5] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [10] FDA Drug Development and Drug Interactions
• [11] Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-Delta(12,14)prostaglandin J2 in MCF7 breast cancer cells. Biochemistry. 2003 May 13;42(18):5429-37.
• [12] Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32.
• [13] ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
• [14] Functional reconstitution of human ABCC3 into proteoliposomes reveals a transport mechanism with positive cooperativity. Biochemistry. 2009 May 26;48(20):4423-30.
• [15] Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702.
• [16] Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102.
• [17] Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch. 2007 Feb;453(5):661-73.
• [18] Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012 Mar;40(3):515-21.
• [19] Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem. 2001 Dec 7;276(49):46400-7.
• [20] Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol. 2008 May;73(5):1474-83.