Drug Information

Drug (ID: DG01634) and It's Reported Resistant Information

• Name: AZD-3759
• Synonyms: AZD3759; 1626387-80-1; zorifertinib; AZD-3759; AZD 3759; (R)-4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl 2,4-dimethylpiperazine-1-carboxylate; UNII-67SX9H68W2; CHEMBL3623290; 67SX9H68W2; 4-[(3-CHLORO-2-FLUOROPHENYL)AMINO]-7-METHOXYQUINAZOLIN-6-YL (2R)-2,4-DIMETHYLPIPERAZINE-1-CARBOXYLATE; (2R)-2,4-dimethyl-1-piperazinecarboxylic acid, 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl ester; [4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl] (2R)-2,4-dimethylpiperazine-1-carboxylate; 4-((3-Chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl (2R)-2,4-dimethylpiperazine-1-carboxylate; SCHEMBL16010006; GTPL10456; EX-A720; AMY10302; BDBM50123453; MFCD29058564; NSC788121; NSC800978; s7971; AKOS027327321; ZINC221149242; CCG-269329; CS-5029; DB14795; NSC-788121; NSC-800978; compound 1m [PMID: 26313252]; NCGC00483922-01; NCGC00483922-02; AC-29957; AS-74755; HY-18750; A882818; (2R)-2,4-Dimethyl-1-piperazinecarboxylic acid 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl ester; (2R)-2,4-Dimethylpiperazine-1-carboxylic acid (4-(2-fluoro-3-chloroanilino)-7-methoxyquinazoline-6-yl) ester; (R)-4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl 2,4-dimethylpiperazine-1-carboxylate
• Target: .; NOUNIPROTAC; [1]
• Formula: 5
• IsoSMILES: C[C@@H]1CN(CCN1C(=O)OC2=C(C=C3C(=C2)C(=NC=N3)NC4=C(C(=CC=C4)Cl)F)OC)C
• InChI: InChI=1S/C22H23ClFN5O3/c1-13-11-28(2)7-8-29(13)22(30)32-19-9-14-17(10-18(19)31-3)25-12-26-21(14)27-16-6-4-5-15(23)20(16)24/h4-6,9-10,12-13H,7-8,11H2,1-3H3,(H,25,26,27)/t13-/m1/s1
• InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
• PubChem CID: 78209992
• DrugBank ID: DB14795

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

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H838 cells; Lung; Homo sapiens (Human); CVCL_1594
• In Vitro Model: NCI-H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NCI-H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay
• Mechanism Description: AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue. Treatment with AZD3759 causes tumor regression in subcutaneous xenograft, leptomeningeal metastasis (LM), and brain metastasis (BM) lung cancer models and prevents the development of BM in nude mice.

References

• Ref 1: AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastasesSci Transl Med. 2016 Dec 7;8(368):368ra172. doi: 10.1126/scitranslmed.aag0976.