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

General Information of Drug (ID: DMDWU1S)

• Drug Name: Rubitecan Drug Info
• Synonyms: 9-Nitrocamptothecin; 91421-42-0; Orathecin; 9-nitro-20(S)-camptothecin; Camptogen; 9-NC; RFS 2000; RFS-2000; UNII-H19C446XXB; Nitrocamptothecin; H19C446XXB; CHEBI:90225; C20H15N3O6; (S)-4-Ethyl-4-hydroxy-10-nitro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; NCGC00167969-01; (s)-4-ethyl-4-hydroxy-10-nitro-1h-pyrano[3',4':6,7]-indolizino[1,2-b]quinoline-3,14(4h,12h)-dione; 9NC; Q-100889; (4s)-4-ethyl-4-hydroxy-10-nitro-1h-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4h,12h)-dione; Inhaled Orathecin; L9NC; Rubitecan (inhaled); Aerosolized liposomal 9 nitro-20 (S) camptothecin; Rubitecan (inhaled), SuperGen; 9-Nitro-20(S)-camptothecin; 9-Nitrocamptothecin (9-NC)

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 472335
  ChEBI ID: CHEBI:90225
  CAS Number: CAS 91421-42-0
  TTD Drug ID: DMDWU1S
  VARIDT Drug ID: DR01438

Molecule-Related Drug Atlas

Drug(s) Transported By Multidrug resistance-associated protein 4 (ABCC4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[5]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[6]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[8]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[4]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[9]
Irinotecan	DMP6SC2	Colorectal cancer	2B91.Z	Approved	[10]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[12]
Ganciclovir	DM1MBYQ	Virus infection	1A24-1D9Z	Approved	[4]

Drug(s) Targeting DNA topoisomerase I (TOP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Colorectal cancer	2B91.Z	Approved	[13]
Topotecan	DMP6G8T	Ovarian cancer	2C73	Approved	[13]
B-Lactams	DMR8YD6	Bacterial infection	1A00-1C4Z	Approved	[14]
Belotecan hydrocholoride	DM3SRJZ	Small-cell lung cancer	2C25.Y	Approved	[15]
Topetecan	DMAE6LK	Small-cell lung cancer	2C25.Y	Approved	[16]
Karenitecin	DMCRGY4	Lung cancer	2C25.0	Phase 3	[17]
Camptothecin	DM6CHNJ	Solid tumour/cancer	2A00-2F9Z	Phase 3	[18]
Exatecan	DMCA7FN	Solid tumour/cancer	2A00-2F9Z	Phase 3	[19]
Edotecarin	DM3ZL7D	Gastric adenocarcinoma	2B72	Phase 3	[20]
Etirinotecan pegol	DMQHX1Y	Breast cancer	2C60-2C65	Phase 3	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase I (TOP1)	TTGTQHC	TOP1_HUMAN	Inhibitor	[2] , [3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[4]

References

• [1] ClinicalTrials.gov (NCT00005869) Nitrocamptothecin Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer. U.S. National Institutes of Health.
• [2] Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.
• [3] A Phase I study of 9-nitrocamptothecin given concurrently with capecitabine in patients with refractory, metastatic solid tumors. Cancer. 2003 Jan 1;97(1):148-54.
• [4] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [5] Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther. 2007 Jan;320(1):229-35.
• [6] Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50.
• [7] ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
• [8] The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9.
• [9] Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J. 2003 Apr 15;371(Pt 2):361-7.
• [10] P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett. 2010 Dec;4(4):195-201.
• [11] Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
• [12] Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem J. 2002 Feb 1;361(Pt 3):497-503.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [14] Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
• [15] Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
• [16] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [17] Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol.2000 Mar;57(3):453-9.
• [18] Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802.
• [19] Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks. Clin Cancer Res. 2001 Dec;7(12):3963-70.
• [20] Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
• [21] Nonclinical pharmacokinetics and activity of etirinotecan pegol (NKTR-102), a long-acting topoisomerase 1 inhibitor, in multiple cancer models. Cancer Chemother Pharmacol. 2014 Dec;74(6):1125-37.