TAZEMETOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C34H44N4O4
Molecular Weight	572.7376
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=NSQSAUGJQHDYNO-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C34H44N4O4
Molecular Weight	572.7376
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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	Inhibitor 7197	Mesothelioma	2.5 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase
Mesothelioma 17	Primary	Histone-lysine N-methyltransferase EZH2	Phase II 1085
Sarcoma, Synovial 5	Primary	Histone-lysine N-methyltransferase EZH2	Phase II 1085
Lymphoma, Large B-Cell, Diffuse 9	Primary	Histone-lysine N-methyltransferase EZH2	Phase II 1085

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 `Mon Oct 21 20:48:21 UTC 2019` Edited by `admin` on `Mon Oct 21 20:48:21 UTC 2019`
Record UNII	Q40W93WPE1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TAZEMETOSTAT

Official Name

English

TAZEMETOSTAT [USAN]

Common Name

English

E-7438

Code

English

EPZ-6438

Code

English

TAZEMETOSTAT [INN]

Common Name

English

TAZEMETOSTAT [WHO-DD]

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

Systematic Name

English

E7438

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)-

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

637118