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

General Information of Drug (ID: DMSKMET)

• Drug Name: Gimatecan Drug Info
• Synonyms: LBQ-707; ST-1480; ST-1481; Camptothecin analogs, Sigma-Tau; 7-cyano-camptothecin

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 9577124
  CAS Number: CAS 292618-32-7
  TTD Drug ID: DMSKMET
  VARIDT Drug ID: DR01339

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	[6]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[6]
B-Lactams	DMR8YD6	Bacterial infection	1A00-1C4Z	Approved	[7]
Belotecan hydrocholoride	DM3SRJZ	Small-cell lung cancer	2C25.Y	Approved	[8]
Topetecan	DMAE6LK	Small-cell lung cancer	2C25.Y	Approved	[9]
Karenitecin	DMCRGY4	Lung cancer	2C25.0	Phase 3	[10]
Camptothecin	DM6CHNJ	Solid tumour/cancer	2A00-2F9Z	Phase 3	[11]
Exatecan	DMCA7FN	Solid tumour/cancer	2A00-2F9Z	Phase 3	[12]
Edotecarin	DM3ZL7D	Gastric adenocarcinoma	2B72	Phase 3	[13]
Rubitecan	DMDWU1S	Human immunodeficiency virus infection	1C62	Phase 3	[14]

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[17]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[18]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[19]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[20]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[21]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]

Drug(s) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[24]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[4]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[25]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[26]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[25]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[27]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[28]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[29]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[30]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[27]

Drug(s) Affected By Cellular tumor antigen p53 (TP53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[31]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[32]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[33]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[34]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[35]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[36]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[37]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[38]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[39]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[40]

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]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[3]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[5]

References

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• [2] Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect. Biochem Pharmacol. 2013 May 15;85(10):1433-40.
• [3] Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
• [4] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [5] Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
• [8] Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [10] 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.
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• [12] 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.
• [13] Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
• [14] Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.
• [15] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [16] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
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• [18] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [19] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
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• [22] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [23] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [24] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [25] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [30] FDA Drug Development and Drug Interactions
• [31] p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer. 2005 Apr 10;114(3):331-6. doi: 10.1002/ijc.20818.
• [32] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [33] Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
• [34] Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
• [35] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [36] Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line. J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. doi: 10.1002/jbt.22638. Epub 2020 Oct 1.
• [37] Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
• [38] 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.
• [39] Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
• [40] Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.