General Information of Drug (ID: DMWO5ZR)

Drug Name
Cediranib
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
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 450.5
Topological Polar Surface Area (xlogp) 4.9
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption
The drug is orally available [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 12 - 35 hours [4]
Chemical Identifiers
Formula
C25H27FN4O3
IUPAC Name
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline
Canonical SMILES
CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NC4=CC(=C(C=C43)OC)OCCCN5CCCC5
InChI
InChI=1S/C25H27FN4O3/c1-16-12-17-19(29-16)6-7-21(24(17)26)33-25-18-13-22(31-2)23(14-20(18)27-15-28-25)32-11-5-10-30-8-3-4-9-30/h6-7,12-15,29H,3-5,8-11H2,1-2H3
InChIKey
XXJWYDDUDKYVKI-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
9933475
ChEBI ID
CHEBI:94782
CAS Number
288383-20-0
DrugBank ID
DB04849
TTD ID
D09VMI
INTEDE ID
DR1886

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 [5], [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Peritoneal cavity cancer
ICD Disease Classification 2C51.Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Vascular endothelial growth factor receptor 2 (KDR) DTT KDR 1.98E-01 0.11 0.2
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 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.
6 Clinical pipeline report, company report or official report of AstraZeneca (2009).
7 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.
8 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.
9 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
10 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.
11 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
12 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.
13 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.
14 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
15 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.
16 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.
17 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.
18 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
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22 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
23 Clinical pipeline report, company report or official report of Exelixis (2011).
24 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
25 Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.