Drug Information

Drug (ID: DG01613) and It's Reported Resistant Information

• Name: Tazemetostat
• Synonyms: Tazemetostat; 1403254-99-8; EPZ-6438; EPZ6438; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide; E7438; UNII-Q40W93WPE1; EPZ 6438; E-7438; Tazemetostat (EPZ-6438); Q40W93WPE1; MFCD24849415; N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide; Tazemetostat [INN]; Tazverik; Tazemetostat [USAN]; Tazemetostat (USAN/INN); Tazemetostat [USAN:INN]; E 7438; Tazemetostat(EPZ-6438); GTPL7011; CHEMBL3414621; SCHEMBL13276848; SCHEMBL19325409; SCHEMBL22210809; EX-A509; HMS3653O07; HMS3747A09; AOB87748; BCP07409; EPZ-7438; 2399AH; NSC777109; NSC791066; s7128; AKOS026750211; ZINC100285161; CCG-264672; CS-1758; DB12887; NSC-777109; NSC-791066; SB22955; NCGC00381562-01; NCGC00381562-10; (1,1'-Biphenyl)-3-carboxamide, N-((1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(4-morpholinylmethyl)-; AC-30931; AS-55991; DA-34776; HY-13803; N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(oxan-4-yl)amino)-4-methyl-4'-((morpholin-4-yl)methyl)(1,1'-biphenyl)-3-carboxamide; QC-11696; SY040988; FT-0700193; SW220030-1; A12712; D11444; J-690163; J-690164; Q27088941; EPZ-6438; EPZ 6438; E7438; Tazemetostat; E-7438; E 7438; (R,Z)-1-(1-(1-(ethylsulfonyl)piperidin-4-yl)ethyl)-N-((2-hydroxy-4-methoxy-6-methylpyridin-3-yl)methyl)-2-methyl-1H-indole-3-carbimi dic acid; 5-(Ethyl(tetrahydro-2H-pyran-4-yl)amino)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl) methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)biphenyl-3-carboxamide; N-[(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-[ethyl(tetrahydropyran-4-yl)amino]-4-methyl-4 inverted exclamation mark -(morpholinomethyl)biphenyl-3-carboxamide
• Indication:
  In total 2 Indication(s)
  Breast cancer [ICD-11: 2C60]; Approved; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [3]
• Target: Fibroblast growth factor receptor (FGFR); NOUNIPROTAC; [3]
• Target: Fibroblast growth factor receptor 1 (FGFR1); FGFR1_HUMAN; [3]
• Target: Fibroblast growth factor receptor 2 (FGFR2); FGFR2_HUMAN; [3]
• Target: Fibroblast growth factor receptor 3 (FGFR3); FGFR3_HUMAN; [3]
• Formula: 9
• IsoSMILES: CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5
• InChI: InChI=1S/C34H44N4O4/c1-5-38(29-10-14-41-15-11-29)32-20-28(27-8-6-26(7-9-27)22-37-12-16-42-17-13-37)19-30(25(32)4)33(39)35-21-31-23(2)18-24(3)36-34(31)40/h6-9,18-20,29H,5,10-17,21-22H2,1-4H3,(H,35,39)(H,36,40)
• InChIKey: NSQSAUGJQHDYNO-UHFFFAOYSA-N
• PubChem CID: 66558664
• TTD Drug ID: D0XT0W
• DrugBank ID: DB12887

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: Histone-lysine N-methyltransferase EZH2 (EZH2) [3]

• Molecule Alteration: Missense mutation; p.Y111D (c.331T>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Pfeiffer cells; Pleural effusion; Homo sapiens (Human); CVCL_3326
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Complex-indel; p.T678_R679delinsKK (c.2032_2037delinsAAGAAG)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: RN2c cells; Blood; Mus musculus (Mouse); N.A.
• In Vitro Model: RN2 cells; Blood; Mus musculus (Mouse); N.A.
• In Vitro Model: Plat-E cells; Fetal kidney; Homo sapiens (Human); CVCL_B488
• Experiment for Molecule Alteration: RT-PCR

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.Y646F (c.1937A>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

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: Rapid generation of drug-resistance alleles at endogenous loci using CRISPR-Cas9 indel mutagenesisPLoS One. 2017 Feb 23;12(2):e0172177. doi: 10.1371/journal.pone.0172177. eCollection 2017.
• Ref 3: Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitorsOncotarget. 2015 Oct 20;6(32):32646-55. doi: 10.18632/oncotarget.5066.