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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