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

General Information of Drug (ID: DMQXYRG)

• Drug Name: 9-AMINOCAMPTOTHECIN Drug Info
• Synonyms: IDEC-132; (S)-10-Amino-4-ethyl-4-hydroxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione; 9-Amino-20(S)-camptothecin

Indication

Disease Entry	ICD 11	Status	REF
Acquired immune deficiency syndrome	1C62.3	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 72402
  ChEBI ID: CHEBI:80755
  CAS Number: CAS 91421-43-1
  TTD Drug ID: DMQXYRG
  VARIDT Drug ID: DR01371
  INTEDE Drug ID: DR1862

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	[5]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[5]
B-Lactams	DMR8YD6	Bacterial infection	1A00-1C4Z	Approved	[6]
Belotecan hydrocholoride	DM3SRJZ	Small-cell lung cancer	2C25.Y	Approved	[7]
Topetecan	DMAE6LK	Small-cell lung cancer	2C25.Y	Approved	[8]
Karenitecin	DMCRGY4	Lung cancer	2C25.0	Phase 3	[9]
Camptothecin	DM6CHNJ	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
Exatecan	DMCA7FN	Solid tumour/cancer	2A00-2F9Z	Phase 3	[11]
Edotecarin	DM3ZL7D	Gastric adenocarcinoma	2B72	Phase 3	[12]
Rubitecan	DMDWU1S	Human immunodeficiency virus infection	1C62	Phase 3	[13]

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	[14]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[15]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[16]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[19]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[21]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[22]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[23]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[24]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[28]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[29]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[30]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[24]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[31]

Drug(s) Metabolized By Cytochrome P450 1A1 (CYP1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[32]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[33]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[34]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[35]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[36]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[37]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[38]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[39]
Riboflavin	DM8YMWE	Acne vulgaris	ED80	Approved	[40]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[41]

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]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Substrate	[4]

References

• [1] ClinicalTrials.gov (NCT00001427) A Phase II Trial of 72-Hour Continuous IV Infusion of 9-Aminocamptothecin With G-CSF Support in Patients With Advanced Ovarian Cancer Previously Treated With Paclitaxel and Cisplatin. U.S. National Institutes of Health.
• [2] Intraperitoneal topoisomerase-I inhibitors. Preliminary findings with 9-aminocamptothecin. Ann N Y Acad Sci. 2000;922:178-87.
• [3] Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
• [4] Cytochrome P450 3A-mediated metabolism of the topoisomerase I inhibitor 9-aminocamptothecin: impact on cancer therapy. Int J Oncol. 2014 Aug;45(2):877-86.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
• [7] Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
• [8] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [9] 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.
• [10] Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802.
• [11] 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.
• [12] Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
• [13] Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.
• [14] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [15] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [16] 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.
• [17] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [18] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [19] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [20] 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.
• [21] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [22] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [23] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [24] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [25] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [26] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [27] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [28] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [29] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [30] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [31] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [32] Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics. 2000 Aug;10(6):519-30.
• [33] Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74.
• [34] Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94.
• [35] Preferred orientations in the binding of 4'-hydroxyacetanilide (acetaminophen) to cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation studies. J Med Chem. 1994 Mar 18;37(6):860-7.
• [36] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [37] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [38] A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med. 2005;43(7):702-6.
• [39] Cytochromes P450 in crustacea. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Nov;121(1-3):157-72.
• [40] Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone. Biochem J. 1998 Apr 1;331 ( Pt 1):273-81.
• [41] Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab. 2007 Aug;8(6):554-62.