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).^[1] It is a EZH2 histone methyltransferase inhibitor.^[2]

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.^[2]

Clinical trials

Mevrometostat in combination with the androgen receptor antagonist enzalutamide in currently in a phase 3 clinical trial for treating advanced prostate cancer.^[3]^[4]

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.

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