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

General Information of Drug (ID: DM9WLN4)

• Drug Name: 10-hydroxycamptothecin Drug Info
• Synonyms: 10-Hydroxycamptothecin; 19685-09-7; (S)-10-Hydroxycamptothecin; Hydroxycamptothecin; 10-hydroxycamptothecine; 10-Hydroxy camptothecin; Hydroxycamptothecine; Camptothecin, hydroxy-; 10-Hydroxy-Camptothecin; (S)-4-Ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; Camptothecin, 10-hydroxy-; Camptothecine, 10-hydroxy-; UNII-9Z01632KRV; NSC 107124; HCPT; (4S)-4-Ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; (S)-10-Hydroxycamptothecin hydrate; NSC107124

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 97226
  ChEBI ID: CHEMBL273862
  CAS Number: CAS 19685-09-7
  TTD Drug ID: DM9WLN4
  VARIDT Drug ID: DR01489

Molecule-Related Drug Atlas

Drug(s) Targeting DNA topoisomerase I (TOP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[4]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[4]
B-Lactams	DMR8YD6	Bacterial infection	1A00-1C4Z	Approved	[5]
Belotecan hydrocholoride	DM3SRJZ	Small-cell lung cancer	2C25.Y	Approved	[6]
Topetecan	DMAE6LK	Small-cell lung cancer	2C25.Y	Approved	[7]
Karenitecin	DMCRGY4	Lung cancer	2C25.0	Phase 3	[8]
Camptothecin	DM6CHNJ	Solid tumour/cancer	2A00-2F9Z	Phase 3	[9]
Exatecan	DMCA7FN	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
Edotecarin	DM3ZL7D	Gastric adenocarcinoma	2B72	Phase 3	[11]
Rubitecan	DMDWU1S	Human immunodeficiency virus infection	1C62	Phase 3	[12]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[14]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[15]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[16]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[2]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[17]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[18]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[20]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[2]

Drug(s) Affected By Bcl-2-like protein 1 (BCL2L1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[23]
Selenium	DM25CGV	N. A.	N. A.	Approved	[24]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[25]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[26]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[27]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[28]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[29]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[30]

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	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Drug Response	[3]

References

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• [2] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [3] siRNA-mediated Bcl-2 and Bcl-xl gene silencing sensitizes human hepatoblastoma cells to chemotherapeutic drugs. Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):450-6. doi: 10.1111/j.1440-1681.2007.04593.x.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
• [6] Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
• [7] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [8] 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.
• [9] Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802.
• [10] 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.
• [11] Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
• [12] Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.
• [13] 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.
• [14] 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.
• [15] ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [22] Expression of the retinoic acid-metabolizing enzyme CYP26A1 limits programmed cell death. Mol Pharmacol. 2005 May;67(5):1808-17. doi: 10.1124/mol.104.005769. Epub 2005 Feb 9.
• [23] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [24] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [25] Role of BAX in the apoptotic response to anticancer agents. Science. 2000 Nov 3;290(5493):989-92. doi: 10.1126/science.290.5493.989.
• [26] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [27] Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. Oncogene. 2005 Feb 10;24(7):1231-43. doi: 10.1038/sj.onc.1208290.
• [28] Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice. Int J Cancer. 2008 Aug 15;123(4):951-7. doi: 10.1002/ijc.23593.
• [29] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [30] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.