Mevrometostat

Mevrometostat
Clinical data
Other names	PF-06821497
Identifiers
	IUPAC name 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1-one;
CAS Number	1844849-10-0;
PubChem CID	118572065;
IUPHAR/BPS	10516;
DrugBank	DB14799;
ChemSpider	65321668;
UNII	S4L4MM20B6;
KEGG	D12845;
ChEBI	CHEBI:756584;
ChEMBL	ChEMBL4080228;
PDB ligand	CJD (PDBe, RCSB PDB);
Chemical and physical data
Formula	C22H24Cl2N2O5
Molar mass	467.34 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=C(C(=O)N1)CN2CCC3=C(C=C(C(=C3C2=O)Cl)[C@@H](C4COC4)OC)Cl)OC;
	InChI InChI=InChI=1S/C22H24Cl2N2O5/c1-11-6-17(29-2)15(21(27)25-11)8-26-5-4-13-16(23)7-14(19(24)18(13)22(26)28)20(30-3)12-9-31-10-12/h6-7,12,20H,4-5,8-10H2,1-3H3,(H,25,27)/t20-/m1/s1; Key:RXCVUHMIWHRLDF-HXUWFJFHSA-N;

Mevrometostat is an investigational new drug that is being evaluated by Pfizer for the treatment of metastatic castration‑resistant prostate cancer (mCRPC). It is a EZH2 histone methyltransferase inhibitor.

Pharmacology

Mevrometostat has sub nanomolar affinity for the Y641N mutant form of EZH2 (which is a proliferation driver mutation). It also has low nanomolar inhibitory potency in reducing H3K27me3 levels and cellular proliferation in cells expressing the Y641N mutation.

Clinical trials

Mevrometostat in combination with the androgen receptor antagonist enzalutamide in currently in a phase 3 clinical trial for treating advanced prostate cancer.

References

↑ "Mevrometostat - Pfizer". AdisInsight. Springer Nature Switzerland AG.
1 2 Kung PP, Bingham P, Brooun A, Collins M, Deng YL, Dinh D, et al. (February 2018). "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)". Journal of Medicinal Chemistry. 61 (3): 650–665. doi:10.1021/acs.jmedchem.7b01375. PMID 29211475.
↑ Clinical trial number NCT07028853 for "This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve." at ClinicalTrials.gov
↑ Ehrlich MI, Gejman RS, Bernstein E, Stein MN (May 2026). "Treatments on the Horizon for Men with Advanced Prostate Cancer". The Urologic Clinics of North America. 53 (2): 331–342. doi:10.1016/j.ucl.2026.02.014. PMID 41986027.

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[1] "Mevrometostat - Pfizer". AdisInsight. Springer Nature Switzerland AG.

[Kung_2018-2] 1 2 Kung PP, Bingham P, Brooun A, Collins M, Deng YL, Dinh D, et al. (February 2018). "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)". Journal of Medicinal Chemistry. 61 (3): 650–665. doi:10.1021/acs.jmedchem.7b01375. PMID 29211475.

[3] Clinical trial number NCT07028853 for "This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve." at ClinicalTrials.gov

[Ehrlich_2026-4] Ehrlich MI, Gejman RS, Bernstein E, Stein MN (May 2026). "Treatments on the Horizon for Men with Advanced Prostate Cancer". The Urologic Clinics of North America. 53 (2): 331–342. doi:10.1016/j.ucl.2026.02.014. PMID 41986027.