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

General Information of Drug (ID: DMW9F1G)

• Drug Name: CKD602 Drug Info
• Synonyms: Belotecan hydrochloride; 213819-48-8; Belotecan; CKD-602; Belotecan HCl; Camtobell hydrochloride; Belotecan (hydrochloride); CKD 602; UNII-01DZ4127G7; 01DZ4127G7; Belotecan hydrochloride (USAN); Belotecan Hydrochloride [USAN]; CHEMBL2107315; DTXSID60175647; BCP28717; HY-13566A; AKOS027420465; API0009359; CS-6955; (S)-4-ethyl-4-hydroxy-11-(2-(isopropylamino)ethyl)-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione hydrochloride; AN-29684; ACM213819488; FT-0662513; D03225; 819C488; J-014022

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 6456014
  ChEBI ID: CHEBI:135702
  CAS Number: CAS 256411-32-2
  TTD Drug ID: DMW9F1G
  VARIDT Drug ID: DR01439

Molecule-Related Drug Atlas

Drug(s) Transported By Multidrug resistance-associated protein 2 (ABCC2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[6]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[7]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[9]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[11]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[12]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[14]

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	[3]
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[15]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[16]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[17]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[16]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[16]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[18]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[21]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[22]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[23]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[24]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[25]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[26]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[27]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[26]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[28]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[29]

Drug(s) Targeting DNA topoisomerase I (TOP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Colorectal cancer	2B91.Z	Approved	[30]
Topotecan	DMP6G8T	Ovarian cancer	2C73	Approved	[30]
B-Lactams	DMR8YD6	Bacterial infection	1A00-1C4Z	Approved	[31]
Belotecan hydrocholoride	DM3SRJZ	Small-cell lung cancer	2C25.Y	Approved	[32]
Topetecan	DMAE6LK	Small-cell lung cancer	2C25.Y	Approved	[33]
Karenitecin	DMCRGY4	Lung cancer	2C25.0	Phase 3	[34]
Camptothecin	DM6CHNJ	Solid tumour/cancer	2A00-2F9Z	Phase 3	[35]
Exatecan	DMCA7FN	Solid tumour/cancer	2A00-2F9Z	Phase 3	[36]
Edotecarin	DM3ZL7D	Gastric adenocarcinoma	2B72	Phase 3	[37]
Rubitecan	DMDWU1S	Human immunodeficiency virus infection	1C62	Phase 3	[38]

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
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[3]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[4]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT00430144) Belotecan (CKD-602) in Recurrent or Progressive Carcinoma of Uterine Cervix. U.S. National Institutes of Health.
• [2] Antitumor activity of 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitor. Arch Pharm Res. 1998 Oct;21(5):581-90.
• [3] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [4] Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells. Pharm Res. 2008 Nov;25(11):2601-12.
• [5] Involvement of the drug transporters p glycoprotein and multidrug resistance-associated protein Mrp2 in telithromycin transport. Antimicrob Agents Chemother. 2006 Jan;50(1):80-7.
• [6] Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61.
• [7] Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
• [8] Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2. Oncol Lett. 2016 Sep;12(3):2107-2114.
• [9] Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
• [10] Lentivirus-mediated RNAi silencing targeting ABCC2 increasing the sensitivity of a human nasopharyngeal carcinoma cell line against cisplatin. J Transl Med. 2008 Oct 4;6:55.
• [11] Effect of acetaminophen on expression and activity of rat liver multidrug resistance-associated protein 2 and P-glycoprotein. Biochem Pharmacol. 2004 Aug 15;68(4):791-8.
• [12] Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7.
• [13] Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63.
• [14] Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
• [15] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [16] 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.
• [17] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [18] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [19] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [20] 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.
• [21] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [22] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [23] The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
• [24] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [25] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [26] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [27] The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
• [28] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [29] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [30] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [31] Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
• [32] Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
• [33] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [34] 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.
• [35] Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802.
• [36] 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.
• [37] Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
• [38] Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.