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

General Information of Drug (ID: DMUJ0W7)

• Drug Name: CP-724714 Drug Info
• Synonyms: CP 724714; CP-724,714; CP724,714, CP-724,714; 2-Methoxy-N-(3-(4-((3-methyl-4-((6-methyl-3-pyridinyl)oxy)phenyl)amino)-6-quinazolinyl)-2-propenyl)acetamide; 2-Methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide

Indication

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 2	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 9874913
  ChEBI ID: CHEBI:91331
  CAS Number: CAS 845680-17-3
  TTD Drug ID: DMUJ0W7
  VARIDT Drug ID: DR01390

Molecule-Related Drug Atlas

Drug(s) Targeting Erbb2 tyrosine kinase receptor (HER2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[5]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[6]
BIBW 2992	DMTKD7Q	Non-small-cell lung cancer	2C25.Y	Approved	[7]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[8]
NERATINIB MALEATE	DMEDU7B	HER2/NEU overexpressing breast cancer	2C60-2C65	Approved	[9]
Margetuximab	DMKEY6S	HER2-positive breast cancer	2C60-2C65	Approved	[10]
Trastuzumab	DMZQOUX	Breast cancer	2C60-2C65	Approved	[11]
Tucatinib	DMBESUA	HER2-positive breast cancer	2C60-2C65	Approved	[12]
Pertuzumab	DMHJV0X	Adrenal gland neoplasm		Approved	[13]
Masoprocol	DMMVNZ0	Prostate cancer	2C82.0	Approved	[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) Affected By Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[24]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[24]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[25]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[26]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[27]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[28]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[30]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[31]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_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 Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Regulation of Drug Effects	[4]

References

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• [2] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [3] Multi-drug-resistance-reverting agents: 2-aryloxazole and 2-arylthiazole derivatives as potent BCRP or MRP1 inhibitors. ChemMedChem. 2009 Feb;4(2):188-95.
• [4] Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714. Toxicol Sci. 2009 Apr;108(2):492-500. doi: 10.1093/toxsci/kfp033. Epub 2009 Feb 17.
• [5] Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7422).
• [7] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [8] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [9] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [11] Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res. 2004 Jun;14(3):207-10.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [13] Clinical pipeline report, company report or official report of Roche (2009).
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [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.
• [17] 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.
• [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.
• [20] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [21] 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.
• [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] Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones. Cell Tissue Res. 2012 Aug;349(2):551-63. doi: 10.1007/s00441-012-1417-5. Epub 2012 May 13.
• [25] Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J Natl Cancer Inst. 2006 Dec 6;98(23):1739-42.
• [26] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [27] ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin. Clin Pharmacol Ther. 2010 May;87(5):558-62.
• [28] Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. Chem Biol Interact. 2016 Apr 25;250:1-11.
• [29] Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
• [30] Activation of beta-catenin signalling by GSK-3 inhibition increases p-glycoprotein expression in brain endothelial cells. J Neurochem. 2008 Aug;106(4):1855-65. doi: 10.1111/j.1471-4159.2008.05537.x. Epub 2008 Jul 4.
• [31] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [32] Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52.