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

General Information of Drug (ID: DMWO5ZR)

• Drug Name: Cediranib Drug Info
• Synonyms: Recentin; AZD 2171; AZD2171; M6294; AZD-2171; ZD-2171; AZD2171, Recentin, Cediranib; Cediranib (USAN/INN); 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline; 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline

Indication

Disease Entry	ICD 11	Status	REF
Peritoneal cavity cancer	2C51.Z	Phase 3	[1] , [2]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 9933475
  ChEBI ID: CHEBI:94782
  CAS Number: CAS 288383-20-0
  TTD Drug ID: DMWO5ZR
  INTEDE Drug ID: DR1886

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[7]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[8]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[9]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[14]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[15]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[16]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[17]
Sunitinib	DMCBJSR	Gastrointestinal cancer	2C11	Approved	[18]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[19]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[20]
Cabozantinib	DMIYDT4	Thyroid cancer	2D10	Approved	[21]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[22]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[23]

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	[3] , [4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[5]

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: 5664).
• [2] ClinicalTrials.gov (NCT02446600) Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. U.S. National Institutes of Health.
• [3] 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.
• [4] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [5] In vitro hepatic metabolism of cediranib, a potent vascular endothelial growth factor tyrosine kinase inhibitor: interspecies comparison and human enzymology. Drug Metab Dispos. 2010 Oct;38(10):1688-97.
• [6] 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.
• [7] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [8] 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.
• [9] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [10] 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.
• [11] 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.
• [12] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [18] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [19] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [20] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [21] Clinical pipeline report, company report or official report of Exelixis (2011).
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [23] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.