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

General Information of Drug (ID: DMMP3Y2)

• Drug Name: YN-968D1 Drug Info
• Synonyms: Apatinib; Apatinib mesylate; VEGF receptor inhibitor (cancer), Advenchen; VEGFR2 receptor inhibitor (cancer), LSK/ Jiangsu Henrui/ Bukwang

Indication

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

• Cross-matching ID:
  PubChem CID: 45139106
  ChEBI ID: CHEMBL3545414
  CAS Number: CAS 1218779-75-9
  TTD Drug ID: DMMP3Y2
  VARIDT Drug ID: DR00819

Molecule-Related Drug Atlas

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[4]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[5]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[6]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[7]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[8]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[9]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[10]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[11]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[12]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[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]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_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] 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: 7648).
• [2] YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.
• [3] Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res. 2010 Oct 15;70(20):7981-91.
• [4] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [5] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [8] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [9] 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.
• [10] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [11] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [12] Clinical pipeline report, company report or official report of Exelixis (2011).
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [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.