Drug Information

Drug (ID: DG01884) and It's Reported Resistant Information

• Name: EZH2 inhibitors
• Synonyms: EZH2 inhibitors
• Target: .; NOUNIPROTAC; [1]

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

Lymphoma [ICD-11: 2A90- 2A85]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [1]

• Molecule Alteration: Missense mutation; p.Y641F (c.1922A>T)
• Sensitive Disease: Lymphoma [ICD-11: 2A90- 2A85]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: CRL-2959 cells; Peritoneal effusion; Homo sapiens (Human); CVCL_2206
• In Vitro Model: CRL-2632 cells; Pleural effusion; Homo sapiens (Human); CVCL_3326
• In Vitro Model: CRL-2631 cells; Peripheral blood; Homo sapiens (Human); CVCL_3611
• In Vitro Model: CRL-2630 cells; Lymph node; Homo sapiens (Human); CVCL_3302
• In Vitro Model: CRL-2261 cells; Ascites; Homo sapiens (Human); CVCL_1660
• In Vitro Model: ACC-576 cells; Pleural effusion; Homo sapiens (Human); CVCL_1889
• In Vitro Model: ACC-575 cells; Pleural effusion; Homo sapiens (Human); CVCL_1902
• In Vitro Model: ACC-528 cells; Bone marrow; Homo sapiens (Human); CVCL_1878
• In Vitro Model: ACC-32 cells; Pleural effusion; Homo sapiens (Human); CVCL_1325
• In Vivo Model: Sprague-Dawley rat model; Rattus norvegicus
• Experiment for Molecule Alteration: ChIP-PCR
• Experiment for Drug Resistance: Cell Titer Glo assay; Tumor volume measurement assay; Immunohistochemistry assay

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [2]

• Molecule Alteration: Missense mutation; p.A677G (c.2030C>G)
• Sensitive Disease: Lymphoma [ICD-11: 2A90- 2A85]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 293 cells; Kidney; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Determination of inhibitor IC50 values in the PMT panel assay
• Mechanism Description: The missense mutation p.A677G (c.2030C>G) in gene EZH2 cause the sensitivity of EZH2 inhibitors by aberration of the drug's therapeutic target

References

• Ref 1: Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphomaMol Cancer Ther. 2014 Apr;13(4):842-54. doi: 10.1158/1535-7163.MCT-13-0773. Epub 2014 Feb 21.
• Ref 2: A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cellsNat Chem Biol. 2012 Nov;8(11):890-6. doi: 10.1038/nchembio.1084. Epub 2012 Sep 30.