Drug Information

Drug (ID: DG01462) and It's Reported Resistant Information

• Name: PD173074
• Synonyms: 219580-11-7; PD173074; PD 173074; PD-173074; 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea; 1-tert-butyl-3-[2-{[4-(diethylamino)butyl]amino}-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea; UNII-A4TLL8634Y; A4TLL8634Y; CHEMBL189584; PD-0173074; CHEBI:63448; C28H41N7O3; MFCD08705327; 1-tert-butyl-3-(2-(4-(diethylamino)butylamino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea; 1-tert-butyl-3-[2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea; 1-tert-butyl-3-[6-(3,5-dimethoxy-phenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea; 3-tert-butyl-1-(2-{[4-(diethylamino)butyl]amino}-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea; 2fgi; SMR000568412; MLS001074892; MLS006011101; SCHEMBL177946; Pyrido[2,3-d]pyrimidine 12; BDBM6190; GTPL5037; AOB2517; DTXSID30176363; EX-A197; SYN1176; BCPP000121; HMS2233G17; HMS3265E09; HMS3265E10; HMS3265F09; HMS3265F10; HMS3371E08; HMS3648A10; HMS3654L09; BCP02368; ZINC3870533; NSC766908; s1264; AKOS016008595; BCP9001065; CCG-264881; CS-0182; NSC-766908; QC-7737; SB19382; NCGC00165863-01; NCGC00165863-02; NCGC00165863-17; AC-24850; AS-16310; BP162784; HY-10321; N-[2-[[4-(Diethylamino)butyl]amino] -6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-y l]-N'-(1,1-dimethylethyl)urea; FT-0673540; P2474; SW218104-2; X7486; PD 173074, >=96% (HPLC), powder; A25450; SR-01000837541; J-014372; J-523314; SR-01000837541-2; Q27088276; FGF/VEGF Receptor Tyrosine Kinase Inhibitor, PD173074 - CAS 219580-11-7; 1-(tert-Butyl)-3-[7-[[4-(diethylamino)butyl]amino]-3-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-2-yl]urea; 1-tert-Butyl-3-(6-(3,5-dimethoxyphenyl)-2-(4-diethylaminobutylamino)pyrido(2,3-d)pyrimidin-7-yl)urea; N-(tert-Butyl)-N -[2-[[4-(diethylamino)butyl]amino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea; N-[2-[[4-(Dethylamno)butyl]amno]-6-(3,5-dmethoxyphenyl)pyrdo[2,3-d ]pyrmdn-7-yl]-n'-(1,1-dmethylethyl)urea; N-[2-[[4-(Diethylamino)butyl]amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)urea; N-[2-[[4-(Diethylamino)butyl]amino]-6-(3,5- dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1- dimethylethyl)urea; N-[2-[[4-(diethylamino)butyl]amino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)-urea; N-[2-[[4-(Diethylamino)butyl]amino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)urea; PD 173074;n-[2-[[4-(diethylamino)butyl]amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-n'-(1,1-dimethylethyl)urea
• Indication:
  In total 1 Indication(s)
  Throat irritation [ICD-11: CA0Z]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [2]
• Target: Long transient receptor potential channel 8 (TRPM8); TRPM8_HUMAN; [2]
• Target: Transformation-sensitive protein p120 (TRPA1); TRPA1_HUMAN; [2]
• Formula: 13
• IsoSMILES: CCN(CC)CCCCNC1=NC2=NC(=C(C=C2C=N1)C3=CC(=CC(=C3)OC)OC)NC(=O)NC(C)(C)C
• InChI: InChI=1S/C28H41N7O3/c1-8-35(9-2)13-11-10-12-29-26-30-18-20-16-23(19-14-21(37-6)17-22(15-19)38-7)25(31-24(20)32-26)33-27(36)34-28(3,4)5/h14-18H,8-13H2,1-7H3,(H3,29,30,31,32,33,34,36)
• InChIKey: DXCUKNQANPLTEJ-UHFFFAOYSA-N
• PubChem CID: 1401
• ChEBI ID: CHEBI:63448
• TTD Drug ID: D04CSZ

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.M536I (c.1608G>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.M536I (c.1608G>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.M538I (c.1614G>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.M538I (c.1614G>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.I548V (c.1642A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.I548V (c.1642A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.N550H (c.1648A>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550H (c.1648A>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.N550S (c.1649A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550S (c.1649A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.N550K (c.1650T>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550K (c.1650T>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.V565I (c.1693G>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.V565I (c.1693G>A) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.E566G (c.1697A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.E566G (c.1697A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.L618M (c.1852T>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.L618M (c.1852T>A) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Rhabdomyosarcoma [ICD-11: 2B55]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 4 (FGFR4) [1]

• Molecule Alteration: Missense mutation; p.N535K (c.1605C>G)
• Sensitive Disease: Alveolar rhabdomyosarcoma [ICD-11: 2B55.0]
• Experimental Note: Identified from the Human Clinical Data

Endometrial cancer [ICD-11: 2C76]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [3]

• Molecule Alteration: Missense mutation; p.N550K (c.1650T>A)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Uterus; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: The missense mutation p.N550K (c.1650T>A) in gene FGFR2 cause the sensitivity of PD173074 by aberration of the drug's therapeutic target

References

• Ref 1: Targeting wild-type and mutationally activated FGFR4 in rhabdomyosarcoma with the inhibitor ponatinib (AP24534)PLoS One. 2013 Oct 4;8(10):e76551. doi: 10.1371/journal.pone.0076551. eCollection 2013.
• Ref 2: The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitorsNeoplasia. 2013 Aug;15(8):975-88. doi: 10.1593/neo.121106.
• Ref 3: Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogationCancer Res. 2008 Sep 1;68(17):6902-7. doi: 10.1158/0008-5472.CAN-08-0770.