Drug Information

Drug (ID: DG01502) and It's Reported Resistant Information

• Name: Cediranib
• Synonyms: Cediranib; 288383-20-0; Recentin; AZD2171; Cedirannib; Cediranib (AZD2171); AZD 2171; AZD-2171; 4-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline; Cediranib free base; 4-(4-Fluoro-2-methylindol-5-yloxy)-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline; Cediranib (AZD217); UNII-NQU9IPY4K9; NQU9IPY4K9; ZD-2171; AZD-2171 maleate; 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; CHEMBL491473; 288383-20-0 (free base); NSC-732208; 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline; C25H27FN4O3; Cediranib (USAN/INN); Cediranib [USAN:INN:BAN]; 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline; Cediranib,AZD2171; Kinome_3318; Cediranib dihydrochloride; AZD2171, Cediranib; Cediranib - AZD2171; SCHEMBL63147; MLS006010063; GTPL5664; QCR-93; CHEBI:94782; AOB1949; DTXSID10183035; BCPP000295; HMS3654G05; HMS3674G17; HMS3744O21; AMY16021; BCP01378; EX-A2039; ZINC3948085; BDBM50331096; MFCD09954115; NSC755606; NSC800069; s1017; AKOS005145767; BCP9000500; CCG-264679; CS-0119; DB04849; ES-0052; NSC-755606; NSC-800069; SB16536; ZD 2171; NCGC00263097-01; NCGC00263097-09; AC-25033; HY-10205; Quinazoline,4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]-; SMR004701223; FT-0751000; SW219261-1; X2636; EC-000.2328; A24280; D08881; Q-101399; Q5057052; BRD-K86930074-001-01-9; 4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1-yl-propoxy)-quinazoline; AV3; Quinazoline, 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(1-pyrrolidinyl)propoxy)-
• Indication:
  In total 2 Indication(s)
  Ovarian cancer [ICD-11: 2C73]; Phase 3; [1]
  Ovarian cancer [ICD-11: 2C73]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Bladder cancer [ICD-11: 2C94]; [1]
• Target: Poly [ADP-ribose] polymerase (PARP); NOUNIPROTAC; [2]
• Formula: 8
• IsoSMILES: 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
• PubChem CID: 9933475
• ChEBI ID: CHEBI:94782
• TTD Drug ID: D01SHZ
• VARIDT ID: DR1886
• DrugBank ID: DB04849

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]

• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]

• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [2]

• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Endometrial cancer [ICD-11: 2C76]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Molecule Alteration: Missense mutation; p.N549K (c.1647T>G)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.N549K (c.1647T>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway

Bladder cancer [ICD-11: 2C94]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]

• Molecule Alteration: Missense mutation; p.Y375C (c.1124A>G)
• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.Y375C (c.1124A>G) in gene FGFR3 cause the resistance of Cediranib by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]

• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway

References

• Ref 1: Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer modelsMol Cancer Ther. 2012 Mar;11(3):690-9. doi: 10.1158/1535-7163.MCT-11-0450. Epub 2012 Jan 11.
• Ref 2: Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinomaCancer Res. 2013 Aug 15;73(16):5195-205. doi: 10.1158/0008-5472.CAN-12-3950. Epub 2013 Jun 20.