Drug Information

Drug (ID: DG01468) and It's Reported Resistant Information

• Name: PD98059
• Synonyms: 167869-21-8; PD 98059; PD98059; 2-(2-amino-3-methoxyphenyl)-4H-chromen-4-one; PD 98,059; PD-98059; 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 2-(2-amino-3-methoxyphenyl)chromen-4-one; 2'-AMINO-3'-METHOXYFLAVONE; PD-098059; 4H-1-Benzopyran-4-one, 2-(2-Amino-3-methoxyphenyl)-; UNII-SJE1IO5E3I; SJE1IO5E3I; CHEMBL35482; C16H13NO3; CHEBI:77954; MFCD00671789; 2-(2-Amino-3-methoxy-phenyl)-chromen-4-one; SR-01000076097; PD 098059; 2-(2-Amino-3-methoxyphenyl)-chromen-4-one; NSC 679829; Tocris-1213; PD098059; Lopac-P-215; BiomolKI_000001; 2-(2-amino-3-methoxy-phenyl)chromen-4-one; BiomolKI2_000011; PD 98,059, solid; Lopac0_001028; BMK1-B1; BSPBio_000996; KBioGR_000336; KBioSS_000336; 2-(2'-amino-3'-methoxyphenyl)oxanaphthalen-4-one; MLS006010134; SCHEMBL157826; 4H-1-Benzopyran-4-one,2-(2-amino-3-methoxyphenyl)-; GTPL5241; QCR-14; 2''-amino-3''-methoxyflavone; BCBcMAP01_000049; KBio2_000336; KBio2_002904; KBio2_005472; KBio3_000671; KBio3_000672; AOB2598; DTXSID40168416; BCPP000123; Bio1_000475; Bio1_000964; Bio1_001453; Bio2_000338; Bio2_000818; HMS1362B17; HMS1792B17; HMS1990B17; HMS3229M08; HMS3263M17; HMS3267D03; HMS3403B17; HMS3412O09; HMS3649N14; HMS3654I16; HMS3676O09; BCP02423; EX-A2127; ZINC1420826; Tox21_501028; BDBM50108771; NSC679828; s1177; AKOS015995212; BCP9001060; BP34124; CCG-100605; CS-0169; LP01028; NSC 679828; NSC-679828; SB16629; SDCCGSBI-0051000.P003; IDI1_002093; SMP2_000052; NCGC00015790-01; NCGC00015790-02; NCGC00015790-03; NCGC00015790-04; NCGC00015790-05; NCGC00015790-06; NCGC00015790-07; NCGC00015790-08; NCGC00025045-01; NCGC00025045-02; NCGC00025045-03; NCGC00025045-04; NCGC00025045-05; NCGC00179347-01; NCGC00261713-01; AC-28412; AS-19374; HY-12028; NCI60_028554; SMR001456459; EU-0101028; FT-0716482; P-215; SW218254-2; X7398; EC-000.2425; A25454; P-4313; PD 98059 & Z-100; InSolution PD 98059 - CAS 167869-21-8; J-505513; SR-01000076097-1; SR-01000076097-3; SR-01000076097-6; 2-(2-amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran; BRD-K62810658-001-05-6; BRD-K62810658-001-06-4; Q27088281; 2-(2-Amino-3-methoxy-phenyl)-chromen-4-one(PD98059); PD 98059 - CAS 167869-21-8; 4H-1-Benzopyran-4-one, 2-(2-amino-3-methoxyphenyl)- & Z-100
• Indication:
  In total 1 Indication(s)
  Spasm [ICD-11: MB47]; 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: Phosphodiesterase 4D (PDE4D); PDE4D_HUMAN; [3]
• Target: Phosphodiesterase 5A (PDE5A); PDE5A_HUMAN; [3]
• Formula: 2
• IsoSMILES: COC1=CC=CC(=C1N)C2=CC(=O)C3=CC=CC=C3O2
• InChI: InChI=1S/C16H13NO3/c1-19-14-8-4-6-11(16(14)17)15-9-12(18)10-5-2-3-7-13(10)20-15/h2-9H,17H2,1H3
• InChIKey: QFWCYNPOPKQOKV-UHFFFAOYSA-N
• PubChem CID: 4713
• ChEBI ID: CHEBI:77954
• TTD Drug ID: D0NJ3V

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 Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.70 Å; PDB: 7B7R
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.01 Å; PDB: 7F2X

RMSD: 2.36; TM score: 0.87257; Amino acid change: C121S

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of PD98059 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) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.53 Å; PDB: 6LVM
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.34 Å; PDB: 4K33

RMSD: 1.24; TM score: 0.96738; Amino acid change: K650E

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: COS-1 cells; Kidney; Chlorocebus aethiops (Green monkey); CVCL_0223
• Experiment for Molecule Alteration: Immunoprecipitation and immunoblot analysis
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of PD98059 by unusual activation of pro-survival pathway

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R834Q (c.2501G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Mechanism Description: The missense mutation p.R834Q (c.2501G>A) in gene FLT3 cause the sensitivity of PD98059 by aberration of the drug's therapeutic target

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]

• Sensitive Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Molecule Alteration: Missense mutation; p.E76K (c.226G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.70 Å; PDB: 5EHR
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.62 Å; PDB: 6CRF

RMSD: 3.04; TM score: 0.6516; Amino acid change: E76K

• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.E76K (c.226G>A) in gene PTPN11 cause the sensitivity of PD98059 by unusual activation of pro-survival pathway

References

• Ref 1: Shp2E76K mutant confers cytokine-independent survival of TF-1 myeloid cells by up-regulating Bcl-XLJ Biol Chem. 2007 Dec 14;282(50):36463-73. doi: 10.1074/jbc.M705789200. Epub 2007 Oct 17.
• Ref 2: Increase in constitutively active MEK1 species by introduction of MEK1 mutations identified in cancersBiochim Biophys Acta Proteins Proteom. 2019 Jan;1867(1):62-70. doi: 10.1016/j.bbapap.2018.05.004. Epub 2018 May 9.
• Ref 3: The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3Oncogene. 2003 Oct 9;22(44):6909-18. doi: 10.1038/sj.onc.1206798.
• Ref 4: Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate allelesCancer Cell. 2007 Dec;12(6):501-13. doi: 10.1016/j.ccr.2007.11.005.