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Stem definition	Drug id	CAS RN
enzyme inhibitors	5380	1403254-99-8

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: tazemetostat tazemetostat hydrobromide tazverik EPZ-6438 EZ438	Tazemetostat is an inhibitor of the methyltransferase, EZH2, and some EZH2 gain-of-function mutations including Y646X and A687V. Tazemetostat also inhibited EZH1 with a half-maximal inhibitory concentration (IC50) of 392 nM, approximately 36 times higher than the IC50 for inhibition of EZH2 Molecular weight: 572.75 Formula: C34H44N4O4 CLOGP: 3.18 LIPINSKI: 1 HAC: 8 HDO: 2 TPSA: 83.14 ALOGS: -4.79 ROTB: 9 Status: OFM Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

tazemetostat
tazemetostat hydrobromide
tazverik
EPZ-6438
EZ438

Tazemetostat is an inhibitor of the methyltransferase, EZH2, and some EZH2 gain-of-function mutations including Y646X and A687V. Tazemetostat also inhibited EZH1 with a half-maximal inhibitory concentration (IC50) of 392 nM, approximately 36 times higher than the IC50 for inhibition of EZH2

Molecular weight: 572.75
Formula: C34H44N4O4
CLOGP: 3.18
LIPINSKI: 1
HAC: 8
HDO: 2
TPSA: 83.14
ALOGS: -4.79
ROTB: 9

Status: OFM

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
S (Water solubility)	0.03 mg/mL	Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
azlogd74	LogD at pH 7.4	3.662		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	14.060		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	23.335	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	35.810	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	10.510	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	23.520	%	High	1
herg	hERG pIC50	4.619	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	12.735	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	187.068	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	7.110	%	High	1
kinase-safety-class	ACVR2B,EIF2AK3,GRK2,PDK1,PDK2,PDK4	6
kinase-selectivity-class	GRK2,PDK1	2
mdck-mdr1-bcrp-efflux	MDCK-MDR1-BCRP efflux ratio	34.995		High	1
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	21.086		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	82.604		High	1
mppb	Mouse plasma protein binding (% unbound)	3.080		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	67.143		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	0
pppb	Pig plasma protein binding (% unbound)	13.360	%	High	1
rat-kpuu-brain	Rat brain Kpuu	0.013	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	62.661	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	33.080	%	High	1
rppb	Rat plasma protein binding (% unbound)	6.050	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	13.836	uM	High	1

Approvals:

Date	Agency	Company	Orphan
June 23, 2021	PMDA	EISAI Co., Ltd.
Jan. 23, 2020	FDA	EPIZYME INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Precursor T-lymphoblastic lymphoma/leukaemia	44.16	42.84	5	298	76	90628068

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	105.57	40.20	40	300	143616	42477379
Malignant pleural effusion	54.80	40.20	10	330	1945	42619050

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	58.65	34.43	28	588	244006	110344677
Product dose omission issue	51.32	34.43	28	588	321754	110266929
Off label use	42.01	34.43	46	570	1500139	109088544
Precursor T-lymphoblastic lymphoma/leukaemia	38.71	34.43	5	611	139	110588544

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01XX72	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Other antineoplastic agents
FDA MoA	N0000191423	Multidrug and Toxin Extrusion Transporter 1 Inhibitors
FDA EPC	N0000193930	Methyltransferase Inhibitor
FDA MoA	N0000193931	Methyltransferase Inhibitors
FDA MoA	N0000193932	Multidrug and Toxin Extrusion Transporter 2 K Inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agent

Related Drugs by ATC class:

L01XX Other antineoplastic agents 33 drugs

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Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Follicular lymphoma	indication	55150002
Epithelioid sarcoma	indication	782827000	DOID:6193

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.8	acidic
pKa2	12.91	acidic
pKa3	6.92	Basic
pKa4	2.4	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10155002	Sept. 12, 2031	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10420775	Sept. 12, 2031	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10420775	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10420775	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	11052093	Sept. 12, 2031	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	11052093	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	11052093	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	12161645	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	12168016	Sept. 12, 2031	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	12168016	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	8691507	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	8765732	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	8765732	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	8895245	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9175331	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9333217	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9334527	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9549931	Sept. 12, 2031	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9549931	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9549931	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9855275	Sept. 12, 2031	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9949999	Sept. 12, 2031	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION BY INHIBITING EZH2
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10245269	April 11, 2033	METHOD OF TREATING EPITHELIOID SARCOMA BY INHIBITING ENHANCER OF ZESTE HOMOLOG 2 (EZH2)
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10245269	April 11, 2033	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA BY INHIBITING EZH2
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10245269	April 11, 2033	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION BY INHIBITING EZH2
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	11491163	April 11, 2033	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	11491163	April 11, 2033	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	11491163	April 11, 2033	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9394283	April 11, 2033	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9394283	April 11, 2033	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	12162865	June 12, 2034	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9688665	Aug. 22, 2034	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10369155	Oct. 16, 2035	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10369155	Oct. 16, 2035	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	10369155	Oct. 16, 2035	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9889138	Oct. 16, 2035	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9889138	Oct. 16, 2035	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	9889138	Oct. 16, 2035	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	12168014	May 3, 2038	METHOD OF TREATING EPITHELIOID SARCOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	12168014	May 3, 2038	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	12168014	May 3, 2038	METHOD OF TREATING RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA POSITIVE FOR AN ENHANCER OF ZESTE HOMOLOG 2 (EZH2) MUTATION

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	Jan. 23, 2027	INDICATED FOR THE TREATMENT OF ADULTS AND PEDIATRIC PATIENTS AGED 16 YEARS AND OLDER WITH METASTATIC OR LOCALLY ADVANCED EPITHELIOID SARCOMA NOT ELIGIBLE FOR COMPLETE RESECTION
EQ 200MG BASE	TAZVERIK	EPIZYME INC	N211723	Jan. 23, 2020	DISCN	TABLET	ORAL	June 18, 2027	INDICATED FOR THE TREATMENT OF ADULT PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA WHOSE TUMORS ARE POSITIVE FOR AN EZH2 MUTATION AS DETECTED BY AN FDA-APPROVED TEST AND WHO HAVE RECEIVED AT LEAST 2 PRIOR SYSTEMIC THERAPIES, AND FOR THE TREATMENT OF ADULT PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA WHO HAVE NO SATISFACTORY ALTERNATIVE TREATMENT OPTIONS

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Histone-lysine N-methyltransferase EZH2	Enzyme	Q15910	EZH2_HUMAN	INHIBITOR	IC50	7.96	DRUG LABEL	DRUG LABEL
Histone-lysine N-methyltransferase EHMT2	Enzyme	Q96KQ7	EHMT2_HUMAN		IC50	8.54	CHEMBL
Polycomb protein EED	Nuclear other	O75530	EED_HUMAN		IC50	8.70	CHEMBL
Histone-lysine N-methyltransferase EZH1	Enzyme	Q92800	EZH1_HUMAN	INHIBITOR	IC50	6.41	DRUG LABEL
Histone-lysine N-methyltransferase EZH2, EC 2.1.1.356	Enzyme		B5DFE2_RAT		IC50	8.40	CHEMBL

External reference:

ID	Source
Q40W93WPE1	UNII
1467052-75-0	SECONDARY_CAS_RN
4039121	VANDF
C4086895	UMLSCUI
CHEMBL3414621	ChEMBL_ID
66558664	PUBCHEM_CID
DB12887	DRUGBANK_ID
CHEMBL4594260	ChEMBL_ID
9963	INN_ID
C000593333	MESH_SUPPLEMENTAL_RECORD_UI
D11444	KEGG_DRUG
7011	IUPHAR_LIGAND_ID
840405005	SNOMEDCT_US
840407002	SNOMEDCT_US
879948007	SNOMEDCT_US
CHEBI:757766	CHEBI
329834	MMSL
37975	MMSL
d09497	MMSL
018265	NDDF
018266	NDDF
2274378	RXNORM
Q40W93WPE1	INXIGHT DRUGS

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
TAZVERIK	HUMAN PRESCRIPTION DRUG LABEL	1	72607-100	TABLET, FILM COATED	200 mg	ORAL	NDA	27 sections

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tazemetostat 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Description:

Drug dosage:

ADMET properties:

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Approvals:

FDA Adverse Event Reporting System (Female)

FDA Adverse Event Reporting System (Male)

FDA Adverse Event Reporting System (Geriatric)

FDA Adverse Event Reporting System (Pediatric)

Pharmacologic Action:

Related Drugs by ATC class:

Drug Use | Suggest Off label Use Form| |View source of the data|

🐶 Veterinary Drug Use

🐶 Veterinary products

Acid dissociation constants calculated using MoKa v3.0.0

Orange Book patent data (new drug applications)

Orange Book exclusivity data (new drug applications)

Bioactivity Summary:

External reference:

Pharmaceutical products: