Details of the Drug

General Information of Drug (ID: DMWP1BH)

Drug Name

Tazemetostat

Synonyms

EPZ-6438; 1403254-99-8; EPZ6438; UNII-Q40W93WPE1; 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; Q40W93WPE1; EPZ 6438; E7438; (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)-

Indication

Disease Entry	ICD 11	Status	REF
Follicular lymphoma	2A80	Approved	[1]
Brain and central nervous system tumour	2A00.11	Phase 2	[2]
Malignant rhabdoid tumour	2A00.1Y	Phase 2	[3]
Mesothelioma	2C51.2	Phase 2	[4]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
Diffuse large B-cell lymphoma	2A81	Phase 1/2	[4]
Synovial sarcoma	2B5A	Phase 1	[4]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

572.7

Topological Polar Surface Area (xlogp)

4.2

Rotatable Bond Count (rotbonds)

9

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

6

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 3340 mcgh/L [5]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 829 mcg/L [5]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1-2 h [5]
Clearance: The total clearance of drug is 274 L/h [5]
Elimination: 15% of drug is eliminated in urine and 79% of drug is eliminated in feces [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 3.1 hours [6]
Metabolism: The drug is metabolized via the CYP3A4 to an inactive desethyl metabolite and one other inactive metabolite [6]
Vd: The volume of distribution (Vd) of drug is 1230 L [5]

Chemical Identifiers

Formula: C34H44N4O4
IUPAC Name: 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
Canonical SMILES: 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

Cross-matching ID

PubChem CID: 66558664
CAS Number: 1403254-99-8
DrugBank ID: DB12887
TTD ID: D00EQL
ACDINA ID: D01463

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Enhancer of zeste homolog 2 (EZH2)	TT9MZCQ	EZH2_HUMAN	Inhibitor	[1]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Tazemetostat (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Tazemetostat caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[14]
Oliceridine	DM6MDCF	Moderate	Increased metabolism of Tazemetostat caused by Oliceridine mediated induction of CYP450 enzyme.	Acute pain [MG31]	[15]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Tazemetostat caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[16]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Tazemetostat caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[16]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Tazemetostat caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Ripretinib	DM958QB	Moderate	Increased metabolism of Tazemetostat caused by Ripretinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[17]
Avapritinib	DMK2GZX	Moderate	Increased metabolism of Tazemetostat caused by Avapritinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[18]
Berotralstat	DMWA2DZ	Major	Decreased metabolism of Tazemetostat caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[16]
Pemigatinib	DM819JF	Moderate	Increased metabolism of Tazemetostat caused by Pemigatinib mediated induction of CYP450 enzyme.	Liver cancer [2C12]	[19]
Selpercatinib	DMZR15V	Moderate	Increased metabolism of Tazemetostat caused by Selpercatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[20]
Ubrogepant	DM749I3	Moderate	Increased metabolism of Tazemetostat caused by Ubrogepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[21]
Darolutamide	DMV7YFT	Moderate	Increased metabolism of Tazemetostat caused by Darolutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[22]
Voxelotor	DMCS6M5	Moderate	Increased metabolism of Tazemetostat caused by Voxelotor mediated induction of CYP450 enzyme.	Sickle-cell disorder [3A51]	[23]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Tazemetostat caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[24]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
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⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Tazemetostat 200 mg tablet	200 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	FDA Approved Drug Products: Tazverik Tazemetostat Oral Tablets
6	Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol. 2018 May;19(5):649-659. doi: 10.1016/S1470-2045(18)30145-1. Epub 2018 Apr 9.
7	Development of new agents for peripheral T-cell lymphoma. Expert Opin Biol Ther. 2019 Mar;19(3):197-209.
8	Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286.
9	ClinicalTrials.gov (NCT04104776) A Study of CPI-0209 in Patients With Advanced Tumors. U.S. National Institutes of Health.
10	Clinical pipeline report, company report or official report of HaiHe Biopharma.
11	National Cancer Institute Drug Dictionary (drug id 756211).
12	Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). J Med Chem. 2018 Feb 8;61(3):650-665.
13	EZH2 inhibitors: a patent review (2014-2016).Expert Opin Ther Pat. 2017 Jul;27(7):797-813.
14	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
15	Bell J, Seres V, Bowron P, Lewis J, Batey R "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther 43 (1988): 623-9. [PMID: 3378383]
16	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
17	Cerner Multum, Inc. "Australian Product Information.".
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Product Information. Pemazyre (pemigatinib). Incyte Corporation, Wilmington, DE.
20	Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
21	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
22	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
23	Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
24	Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.