TAZEMETOSTAT HYDROBROMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C34H44N4O4.BrH
Molecular Weight	653.65
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Br.CCN(C1CCOCC1)C2=C(C)C(=CC(=C2)C3=CC=C(CN4CCOCC4)C=C3)C(=O)NCC5=C(C)C=C(C)NC5=O

InChI

InChIKey=UQRICAQPWZSJNF-UHFFFAOYSA-N

InChI=1S/C34H44N4O4.BrH/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);1H

HIDE SMILES / InChI

Molecular Formula	BrH
Molecular Weight	80.912
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C34H44N4O4
Molecular Weight	572.7376
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24563539 | http://www.epizyme.com/wp-content/uploads/2015/12/Tazemetostat-ASH2015.pdf

Tazemetostat (EPZ-6438) is a selective inhibitor of histone-lysine N-methyltransferase EZH2. The drug is under clinical development (phase II) for the treatment of Diffuse Large B Cell Lymphoma, Malignant Mesothelioma and Synovial Sarcoma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histone-lysine N-methyltransferase EZH2 10 Target ID: CHEMBL2189110 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24563539	Inhibitor 8297		2.5 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Malignant mesothelioma 6 Sources: https://clinicaltrials.gov/ct2/show/NCT02860286	Primary	Phase II 1132	Unknown Approved Use Unknown
Synovial sarcoma 7 Sources: https://clinicaltrials.gov/ct2/show/NCT02601950	Primary	Phase II 1132	Unknown Approved Use Unknown
Diffuse large B-cell lymphoma 20 Sources: https://clinicaltrials.gov/ct2/show/NCT02889523	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
818 ng/mL REVIEW https://patents.google.com/patent/WO2017079757A1	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAZEMETOSTAT unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4630 ng × h/mL REVIEW https://patents.google.com/patent/WO2017079757A1	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TAZEMETOSTAT unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 2 times / day steady, oral Studied dose Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29650362/	unhealthy, 38 - 70 years n = 64 Health Status: unhealthy Condition: B-cell non-Hodgkin lymphoma or Solid tumour Age Group: 38 - 70 years Sex: M+F Population Size: 64 Sources: https://pubmed.ncbi.nlm.nih.gov/29650362/	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 1 patient) Thrombocytopenia (grade 4, 1 patient) Alanine aminotransferase increased (grade 4) Aspartate aminotransferase increase (grade 4) Fatigue (grade 3) Cardiotoxicity (grade 2) Nausea (grade 3) Vomiting (grade 3) Diarrhoea (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/29650362/
1600 mg 2 times / day multiple, oral Highest studied dose Dose: 1600 mg, 2 times / day Route: oral Route: multiple Dose: 1600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf Page: 89	unhealthy, adult n = 64 Health Status: unhealthy Condition: epithelioid sarcoma Age Group: adult Sex: unknown Population Size: 64 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf Page: 89	DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf Page: 89
1600 mg 2 times / day single, oral Highest studied dose Dose: 1600 mg, 2 times / day Route: oral Route: single Dose: 1600 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29650362/	unhealthy, adult n = 1 Health Status: unhealthy Condition: B-cell non-Hodgkin lymphoma or Solid tumour Age Group: adult Sex: unknown Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29650362/	DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/29650362/
800 mg 2 times / day multiple, oral Recommended Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: 6.1	unhealthy, adult n = 62 Health Status: unhealthy Condition: epithelioid sarcoma Age Group: adult Sex: unknown Population Size: 62 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: 6.1	Disc. AE: Mood disorder NOS... Other AEs: Decreased appetite... AEs leading to discontinuation/dose reduction: Mood disorder NOS (2%) Other AEs: Decreased appetite (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: 6.1
800 mg 2 times / day multiple, oral Recommended Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: Table 4	unhealthy, adult n = 62 Health Status: unhealthy Condition: epithelioid sarcoma Age Group: adult Sex: unknown Population Size: 62 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: Table 4	Disc. AE: Mood disorder NOS... Other AEs: Pain, Fatigue... AEs leading to discontinuation/dose reduction: Mood disorder NOS (2%) Other AEs: Pain (all grades, 52%) Fatigue (all grades, 47%) Nausea (all grades, 36%) Vomiting (all grades, 24%) Constipation (all grades, 21%) Diarrhea (all grades, 16%) Abdominal pain (all grades, 13%) Decreased appetite (all grades, 26%) Cough (all grades, 18%) Dyspnea (all grades, 16%) Hemorrhage (all grades, 18%) Headache (all grades, 18%) Anemia (all grades, 16%) Weight decreased (all grades, 16%) Pain (grade 3-4, 7%) Fatigue (grade 3-4, 1.6%) Abdominal pain (grade 3-4, 1.6%) Decreased appetite (grade 3-4, 4.8%) Dyspnea (grade 3-4, 4.8%) Hemorrhage (grade 3-4, 4.8%) Anemia (grade 3-4, 13%) Weight decreased (grade 3-4, 7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: Table 4
800 mg 2 times / day multiple, oral Recommended Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: Table 5	unhealthy, adult n = 62 Health Status: unhealthy Condition: epithelioid sarcoma Age Group: adult Sex: unknown Population Size: 62 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: Table 5	Other AEs: Decreased hemoglobin, Lymphocyte count decreased... Other AEs: Decreased hemoglobin (all grades, 49%) Lymphocyte count decreased (all grades, 36%) White blood cell count decreased (all grades, 19%) Triglyceride increased (all grades, 36%) Glucose increased (all grades, 33%) Sodium decreased (all grades, 30%) Phosphate decreased (all grades, 28%) Albumin decreased (all grades, 23%) Alkaline phosphatase increased (all grades, 23%) Potassium decreased (all grades, 20%) Aspartate aminotransferase increased (all grades, 18%) Calcium decreased (all grades, 16%) Glucose decreased (all grades, 16%) Partial thromboplastin time prolonged (all grades, 15%) Alanine aminotransferase increased (all grades, 14%) Creatinine increased (all grades, 12%) Potassium increased (all grades, 12%) Decreased hemoglobin (grade 3-4, 15%) Lymphocyte count decreased (grade 3-4, 13%) Triglyceride increased (grade 3-4, 3.3%) Glucose increased (grade 3-4, 1.6%) Sodium decreased (grade 3-4, 1.7%) Phosphate decreased (grade 3-4, 1.7%) Alkaline phosphatase increased (grade 3-4, 1.7%) Potassium decreased (grade 3-4, 1.7%) Aspartate aminotransferase increased (grade 3-4, 3.5%) Partial thromboplastin time prolonged (grade 3-4, 5%) Alanine aminotransferase increased (grade 3-4, 3.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211723s000lbl.pdf Page: Table 5

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 CYP1A2 1524 CYP2B6 810 MATE1 306 MATE2 263 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647 OAT1 599 OAT3 642 BSEP 402	CYP3A 191 P-gp 1537 BCRP 561 OCT2 355 OAT3 339 MATE1 135 OATP1B1 406 OATP1B3 350	CYP3A 129 CYP1A2 701 CYP2B6 547 CYP2C8 168 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >10 uM]	EPZ-6930 5
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >20 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no [IC50 >20 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ-6930 5
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ006931 5
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ034163 5
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ-6930 5
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ006931 5
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ034163 5
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ-6930 5
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ006931 5
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ034163 5
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ-6930 5
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ006931 5
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ034163 5
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ-6930 5
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ006931 5
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ034163 5
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ-6930 5
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ006931 5
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ034163 5
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ-6930 5
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ006931 5
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	no	EPZ034163 5
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	weak
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	weak
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	weak
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	weak
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	weak
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 1.27 uM]		yes (co-administration study) Comment: Coadministration of tazemetostat 800 mg BID with an oral cocktail of repaglinide (a sensitive CYP2C8 substrate) and omeprazole (a sensitive CYP2C19 substrate) in patients increased repaglinide Cmax by 51% and AUClast by 80%; and decreased omeprazole Cmax by 18% and AUClast by 20% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 1.89 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 12.1 uM]	EPZ-6930 5
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 15 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 2.65 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 3.06 uM]		yes (co-administration study) Comment: Coadministration of tazemetostat 800 mg BID with an oral cocktail of repaglinide (a sensitive CYP2C8 substrate) and omeprazole (a sensitive CYP2C19 substrate) in patients increased repaglinide Cmax by 51% and AUClast by 80%; and decreased omeprazole Cmax by 18% and AUClast by 20% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 4.79 uM]	EPZ-6930 5
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 6.65 uM]		yes (co-administration study) Comment: In patients with cancer, coadministration of tazemetostat 800 mg BID with single oral doses of repaglinide (0.25 mg, a sensitive CYP2C8 substrate) and omeprazole (20 mg, a sensitive CYP2C19 substrate) increased repaglinide Cmax by 50% and AUCinf by 80%, Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes [IC50 9.16 uM]
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=87 Page: 87.0	major
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=78 Page: 78.0	major	yes (co-administration study) Comment: Coadministration of fluconazole (a moderate CYP3A inhibitor) with tazemetostat 400 mg twice daily increased tazemetostat steady-state AUClast in patients by 3.1-fold and Cmax by 2.3-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=78 Page: 78.0
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=86 Page: 86.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=86 Page: 86.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=86 Page: 86.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=86 Page: 86.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=86 Page: 86.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=86 Page: 86.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=97 Page: 97.0	yes	unlikely Comment: Therefore, P-gp is expected to play a minor role in regulating tazemetostat absorption and the P-gp-mediated DDI risk at intestinal absorption is low for tazemetostat as a victim drug Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=97 Page: 97.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf#page=32 Page: 32.0

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific, Inc. (AKSCI)	2399AH	http://www.aksci.com/item_detail.php?cat=2399AH
AbMole Bioscience	M2677	http://www.abmole.com/products/epz-6438.html
Achemtek	0102-012746	http://www.achemtek.com/1403254-99-8
Acorn PharmaTech	ACN-029397	http://www.acornpharmatech.com/
Active Biopharma	ABP001111	http://www.activebiopharma.com/1403254-99-8
Adooq BioScience	A12712	https://www.adooq.com/epz-6438.html
Ambinter	Amb24059721	http://www.ambinter.com/reference/24059721
Angene	AGN-PC-0WH9N3	http://www.angenechemical.com/productshow/AGN-PC-0WH9N3.html
ApexBio Technology	A8221	http://www.apexbt.com/epz-6438.html
Ark Pharm	AK317596	http://www.arkpharminc.com/products/1403254-99-8.html
Ark Pharma Scientific Limited	A-1248	http://www.arkpharmtech.com/product/33199.html
Aurora Fine Chemicals LLC	K16.667.108	http://online.aurorafinechemicals.com/info?ID=K16.667.108
Axon MedChem	2227	https://www.axonmedchem.com/product/2227
BOC Sciences	1403254-99-8	https://www.bocsci.com/epz-6438-cas-1403254-99-8-item-84-462339.html
BioChemPartner	BCP07409	http://www.biochempartner.com/1403254-99-8-BCP07409
BioCrick	BCC3634	http://www.biocrick.com/EPZ-6438-BCC3634.html
BioSynth	J-690163	https://www.biosynth.com/en/products/all-products/products/J-690184.html
BioSynth	J-690164	https://www.biosynth.com/en/products/all-products/products/J-690185.html
Boerchem	BC600303	http://www.boerchem.com/?product_43138.html
Chem Scene	CS-1758	http://www.chemscene.com/1403254-99-8.html
ChemieTek	CT-EPZ438	http://www.chemietek.com/epz-6438-details.aspx
Chemspace	CSSB00015190551	https://chem-space.com/CSSB00015190551
Clearsynth	CS-T-92516	https://www.clearsynth.com/en/CST92516.html
DC Chemicals	DC7122	http://www.dcchemicals.com/product_show-Tazemetostat_EPZ_6438_.html
Debye Scientific	DA-34776	http://www.debyesci.com/cas_1403254-99-8.html
Excenen	EX-A509	http://www.excenen.com/searchresultlist.php?id=1403254-99-8
Finetech	FT-0700193	http://www.finetechnology-ind.com/prod/detail/pub/1403254-99-8.html
Lab Network	LN01297365	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01297365
Matrix Scientific	147189	https://www.matrixscientific.com/147189.html
MedChem Express	HY-13803	https://www.medchemexpress.com/EPZ-6438.html
Smolecule	S544620	http://www.smolecule.com/products/s544620
Synblock Inc	SB22955	http://www.synblock.com/product/1403254-99-8.html
THE BioTek	bt-283516	https://www.thebiotek.com/product/inhibitors/bt-283516
abcr GmbH	AB479418	http://www.abcr.com/shop/en/AB479418
eNovation Chemicals	Y0975468	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0975468
iChemical	EBD2207002	http://www.ichemical.com/products/1403254-99-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
		252160839
Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2.	2013 May 7	23620515

Patents

Sample Use Guides

In Vivo Use Guide

Malignant Mesothelioma, Synovial Sarcoma: patients receive 800 mg of oral tazemetostat two times daily. Diffuse Large B Cell Lymphoma: patients receive 200, 400, 600 or 800 mg of the drug twice a day in combination with rituximab (IV, 375 mg/m2, day 1),pPrednisolone (PO, 40 mg/m2 in the morning, day 1 to day 5), doxorubicine (IV, 50 mg/m2, day 1), cyclophosphamide (IV, 750 mg/m2, day 1), vincristine (IV, 1.4 mg/m2, day 1): 8 cycles, every 21 days.

Route of Administration: Oral

In Vitro Use Guide

Treatment of WSU-DLCL2 with 1uM tazemetostat for 4 days resulted in a concentration-dependent reduction in global H3K27Me3 levels with an IC50 value of 9 nmol/L. Treatment of WSU-DLCL2 cells with 200 nM tazemetostat; KARPAS-422 with 100 nM; SU-DHL-6 with 200 nM; and Pfeiffer with 0.5 nM inhibited cell proliferation with IC50 values of 0.0086, 0.0018, 0.0047 and 0.00049 uM, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 06:18:18 GMT 2023` Edited by `admin` on `Sat Dec 16 06:18:18 GMT 2023`
Record UNII	6P89T5M073
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TAZEMETOSTAT HYDROBROMIDE

Official Name

English

TAZEMETOSTAT MONOHYDROBROMIDE

Common Name

English

TAZVERIK

Brand Name

English

EPZ-6438 MONOHYDROBROMIDE

Code

English

TAZEMETOSTAT HYDROBROMIDE [JAN]

Common Name

English

Tazemetostat hydrobromide [WHO-DD]

Common Name

English

TAZEMETOSTAT HYDROBROMIDE [ORANGE BOOK]

Common Name

English

TAZEMETOSTAT HYDROBROMIDE [USAN]

Common Name

English

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 MONOHYDROBROMIDE

Systematic Name

English

E-7438 HYDROBROMIDE

Code

English

EZ438

Code

English

EZ-438

Code

English

(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)-, HYDROBROMIDE (1:1)

Systematic Name

English

Code System Code Type Description

RXCUI

2274379