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Table 3 PKMT inhibitors in various stages of clinical development

From: Clinicopathologic significance of protein lysine methyltransferases in cancer

EZH2

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

Tazemetostat (EPZ-6438, Epizyme)

SAM-competitive

Hematologic malignancies:

-Tazemetostat monotherapy: NCT03009344, NCT03456726, NCT02220842 (completed)

-Tazemetostat in combination: NCT04224493 (Tazemetostat + Lenalidomide/Rituximab)

Hematologic + solid tumors:

-Tazemetostat monotherapy: NCT02875548, NCT03010982 (completed), NCT01897571, NCT03213665,

NCT03028103, NCT03155620

Solid tumors:

-Tazemetostat monotherapy: NCT02601950, NCT02860286 (completed), NCT04241835, NCT02601937

-Tazemetostat in combination: NCT04179864 (Tazemetostat + Abiraterone/Enzalutamide), NCT04204941 (Tazemetostat + Doxorubicin), NCT03854474 (Tazemetostat + Pembrolizumab)

GSK2816126 (GlaxoSmithKline)

SAM-competitive inhibition (PRC2-specific inhibitor)

1 terminated trial

CPI-1205

(Constellation Pharmaceuticals)

SAM-competitive inhibition (PRC2-specific inhibitor)

Hematologic malignancies:

-CPI-1205 monotherapy: NCT02395601 (completed)

Solid tumors:

-CPI-1205 in combination: NCT03480646 (CPI-1205 + Abiraterone/Enzalutamide), NCT03525795 (CPI-1205 + Ipilimumab)

MAK683 (Novartis)

PRC2 complex disruptor (binds to EED)

Hematologic malignancies:

-MAK683 monotherapy: NCT02900651

PRC2 Complex

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

SAH-EZH2

(Calbiochem)

Disruption of PRC2 subunit interactions

Preclinical use

A-395

Disruption of PRC2 subunit interactions

Preclinical use

EZH1/EZH2

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

Valemetostat

(DS-3201b, Daiichi Sankyo)

EZH1/EZH2 inhibitor with equal affinity via SAM-competitive inhibition

Hematologic malignancies:

-Valemetostat monotherapy: NCT03110354, NCT04102150, NCT02732275

Solid tumors:

-Valemetostat in combination: NCT03879798 (Valemetostat + Irinotecan), NCT04388852 (Valemetostat + Ipilimumab)

Hepatic impairment:

-Valemetostat monotherapy: NCT04276662

899145

SAM-competitive inhibition

Preclinical use

DOT1L

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

Pinometostat (EPZ-5676, Epizyme)

SAM-competitive inhibition

Hematologic malignancies:

-Pinometostat in combination: NCT03701295 (Pinometostat + Azacitidine), NCT03724084 (Pinometostat + Cytarabine/Daunorubicin/Daunorubicin Hydrochloride)

Menin-MLL

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

MI-503

Disruption of MLL complex subunit interactions

Preclinical use

EHMT1/EHMT2

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

UNC0642

Peptide-competitive inhibitor

Preclinical use

SUV420H1/2

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

A-196

Peptide-competitive inhibitor

Preclinical use

SMYD2

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

EPZ033294

Peptide-competitive inhibitor

Preclinical use

SMYD3

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

EPZ031686

Peptide-competitive inhibitor

Preclinical use

SETD7

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

(R)-PFI-2

Peptide-competitive inhibitor

Preclinical use

SETD8

Compound name

Mechanism of action

Clinical trial information (clinicaltrials.gov)

UNC0379

Peptide-competitive inhibitor

Preclinical use