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

General Information of Drug (ID: DM20ATW)

• Drug Name: DIFLOMOTECAN Drug Info
• Synonyms: BN-80915; R-1536; Diflomotecan; (+)-5(R)-Ethyl-9,10-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione

Indication

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

• Cross-matching ID:
  PubChem CID: 219023
  ChEBI ID: CHEBI:144046
  CAS Number: CAS 220997-97-7
  TTD Drug ID: DM20ATW
  VARIDT Drug ID: DR01498

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 Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[15]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[16]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[18]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[19]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[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]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT00080015) Diflomotecan (BN80915) Administered Once Every 3 Weeks in Treating Patients With Sensitive Small Cell Lung Cancer (SCLC). U.S. National Institutes of Health.
• [2] Diflomotecan, a promising homocamptothecin for cancer therapy. Expert Opin Investig Drugs. 2009 Jan;18(1):69-75.
• [3] Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
• [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] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [14] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [15] 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.
• [16] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [17] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [18] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [19] 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.
• [20] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [21] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.