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

General Information of Drug (ID: DMRKE63)

• Drug Name: Chlorambucil Drug Info
• Synonyms: Ambochlorin; Amboclorin; Chlocambucil; Chloorambucol; Chlorambucilum; Chloraminophen; Chloraminophene; Chlorbutin; Chlorbutine; Chlorbutinum; Chloroambucil; Chlorobutin; Chlorobutine; Clorambucile; Clorambucilo; Ecloril; Elcoril; Elcorin; Leukeran; Leukersan; Leukoran; Linfolizin; Linfolysin; Lympholysin; Clorambucile [DCIT]; Glaxo Wellcome Brand of Chlorambucil; GlaxoSmithKline Brand of Chlorambucil; Leuk ersan; Leukeran tablets; Phenylbutyric acid nitrogen mustard; Wellcome Brand of Chlorambucil; C0253; CB 1348; CB1348; Cb l348; CB-1348; Chlorambucil [INN:BAN]; Chlorambucilum [INN-Latin]; Clorambucilo [INN-Spanish]; LEUKERAN (TN); Leukeran (TN); Phenylbuttersaeure-lost; Phenylbuttersaeure-lost[German]; Chlorambucil (USP/INN)

Indication

Disease Entry	ICD 11	Status	REF
Chronic lymphocytic leukaemia	2A82.0	Approved	[1] , [2]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 2708
  ChEBI ID: CHEBI:28830
  CAS Number: CAS 305-03-3
  TTD Drug ID: DMRKE63
  VARIDT Drug ID: DR00895
  INTEDE Drug ID: DR0297
  ACDINA Drug ID: D00119

Molecule-Related Drug Atlas

Drug(s) Metabolized By Glutathione S-transferase pi (GSTP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[9]
Carboplatin	DMG281S	Ovarian cancer	2C73	Approved	[9]
Busulfan	DMXYJ9C	Myeloproliferative syndrome	2A22	Approved	[10]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Bacterial infection	1A00-1C4Z	Approved	[11]
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[5]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[13]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[5]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]

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	[17]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Atorvastatin	DMF28YC	Cardiovascular disease	BA00-BE2Z	Approved	[20]
Pitavastatin calcium	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[21]
Rosuvastatin	DMMIQ7G	Hypercholesterolaemia	5C80.0	Approved	[22]
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[23]
Enalapril	DMNFUZR	Hypertension	BA00-BA04	Approved	[24]
Cholic acid	DM7OKQV	Peroxisomal disorder	5C57	Approved	[25]
Liothyronine	DM6IR3P	Hypothyroidism	5A00	Approved	[26]

Drug(s) Targeting DNA replication (DNA repli)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daunorubicin	DMQUSBT	Acute myeloid leukaemia	2A60	Approved	[27]
Ozenoxacin	DM6KZMG	Impetigo	1B72	Approved	[28]
Elliptinium acetate	DMZC6GT	Solid tumour/cancer	2A00-2F9Z	Approved	[29]
DFP-10917	DM1WNGJ	Acute myeloid leukaemia	2A60	Phase 3	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA replication (DNA repli)	TTABD5E	NOUNIPROTAC	Intercalator	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[4]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Glutathione S-transferase pi (GSTP1) Main DME	DEK6079	GSTP1_HUMAN	Substrate	[6]

References

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• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010669.
• [3] Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A. Mol Cancer Ther. 2009 Jun;8(6):1714-23.
• [4] Transporters and renal drug elimination. Annu Rev Pharmacol Toxicol. 2004;44:137-66.
• [5] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [6] The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol. 2008 Jun 27;380(1):131-44.
• [7] Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. Anticancer Drugs. 2000 Sep;11(8):639-43.
• [8] Reactions of glutathione with the catechol, the ortho-quinone and the semi-quinone free radical of etoposide. Consequences for DNA inactivation. Biochem Pharmacol. 1992 Apr 15;43(8):1761-8.
• [9] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [10] Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos. 1996 Sep;24(9):1015-9.
• [11] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [12] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [13] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [14] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [15] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [16] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [17] Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
• [18] 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.
• [19] Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
• [20] 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.
• [21] Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
• [22] Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
• [23] 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.
• [24] 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.
• [25] Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82.
• [26] Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
• [27] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [28] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [29] Stationary potential of the brain: Part II. Clinical studies. Neurol Med Chir (Tokyo). 1979 Jul;19(7):655-64.
• [30] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)