Drug Information

Drug (ID: DG01626) and It's Reported Resistant Information

• Name: Naquotinib
• Synonyms: Naquotinib; 1448232-80-1; ASP8273; UNII-47DD4548PB; 2-Pyrazinecarboxamide, 6-ethyl-3-[[4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[[(3R)-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]oxy]-; 47DD4548PB; ASP-8273; 6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide; (R)-5-((1-acryloylpyrrolidin-3-yl)oxy)-6-ethyl-3-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrazine-2-carboxamide; e-2-carboxamide; 2-Pyrazinecarboxamide, 6-ethyl-3-((4-(4-(4-methyl-1-piperazinyl)-1-piperidinyl)phenyl)amino)-5-(((3R)-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl)oxy)-; Naquotinib [USAN]; Naquotinib (USAN/INN); ASP8273 (Naquotinib); Naquotinib; ASP-8273; GTPL9248; CHEMBL3663929; SCHEMBL16196078; BDBM170514; EX-A2669; YHC23280; NSC793322; s8412; ZINC205341959; CCG-270060; CS-5469; DB12036; NSC-793322; AS-75247; HY-19729; J3.496.214F; A14408; C91356; D10958; US9085540, 54; A857977; Q27074546; 5-[[(3R)-1-Acryloylpyrrolidine-3-yl]oxy]-6-ethyl-3-[4-[4-(4-methylpiperazine-1-yl)piperidino]anilino]pyrazine-2-carboxamide; 6-Ethyl-3-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)-5-(((3R)-1-(1-oxoprop-2-en-1-yl)pyrrolidin-3-yl)oxy)pyrazine-2-carboxamide; 6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-{[(3R)-1-(prop-2-enoyl)pyrrolidin-3-yl]oxy}pyrazine-2-carboxamide; 6-Ethyl-3-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)anilino)-5-(((3R)-1-(prop-2-enoyl)pyrrolidin-3-yl)oxy)pyrazine-2-carboxamide; 6-Ethyl-3-[[4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[[(3R)-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]oxy]-2-pyrazinecarboxamide; 6-ethyl-3-[[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]amino]-5-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxy-pyrazin
• Indication:
  In total 1 Indication(s)
  Coronavirus Disease 2019 (COVID-19) [ICD-11: 1D6Y]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [1]
• Target: .; NOUNIPROTAC; [1]
• Formula: 9
• IsoSMILES: CCC1=C(N=C(C(=N1)C(=O)N)NC2=CC=C(C=C2)N3CCC(CC3)N4CCN(CC4)C)O[C@@H]5CCN(C5)C(=O)C=C
• InChI: InChI=1S/C30H42N8O3/c1-4-25-30(41-24-12-15-38(20-24)26(39)5-2)34-29(27(33-25)28(31)40)32-21-6-8-22(9-7-21)36-13-10-23(11-14-36)37-18-16-35(3)17-19-37/h5-9,23-24H,2,4,10-20H2,1,3H3,(H2,31,40)(H,32,34)/t24-/m1/s1
• InChIKey: QKDCLUARMDUUKN-XMMPIXPASA-N
• PubChem CID: 71667668
• TTD Drug ID: D0GT5W
• DrugBank ID: DB12036

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

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

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: IF-insertion; p.Y764_V765insHH (c.2292_2293insCATCAT)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Complex-indel; p.L747_P753delinsS (c.2240_2257del18)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Duplication; p.A767_V769 (c.2299_2307)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: IF-insertion; p.P772_H773insGNP (c.2316_2317insGGTAACCCT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: IF-deletion; p.E746_A750delELREA (c.2236_2250del15)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

References

• Ref 1: Pharmacological and Structural Characterizations of Naquotinib, a Novel Third-Generation EGFR Tyrosine Kinase Inhibitor, in EGFR-Mutated Non-Small Cell Lung CancerMol Cancer Ther. 2018 Apr;17(4):740-750. doi: 10.1158/1535-7163.MCT-17-1033. Epub 2018 Feb 21.