Table 1.
List of degraders and inhibitors of PKMTs reported in last several years.
| Methylation Mark | Target Protein | Compound Name | Mode of Action | Tumor Type (Cell Lines) | In Vivo |
|---|---|---|---|---|---|
| H3K27me3 | EED | UNC6582 | PROTAC (VHL) | DLBCL (DB, Pfieffer) Other: HeLa |
|
| EED | PROTAC 1 | PROTAC (VHL) | DLBCL (Karpas422) | ||
| EZH2 | MS1943 | Hydrophobic tag | TNBC (MDA-MB-468, BT549, HCC70, MDA-MB-231, HCC1187, HCC70, HCC1954) DLBCL (Karpas422, SUDHL8) Other: PNT2, MCF7, K562, A549, HCC827, MCF10A |
Y | |
| EZH2 | MS8815 | PROTAC (VHL) | TNBC (MDA-MB-453, BT549, SUM159, MDA-MB-468, 515a*) | Y | |
| EZH2 | YM281 | PROTAC (VHL) | Lymphoma (SU-DHL-2, SU-DHL-4, SU-DHL-6) Other: 22Rv1 |
Y | |
| EZH2 | U3i | PROTAC (VHL) | TNBC (MDA-MB-231, MDA-MB-468, BT549) Leukemia (MV4;11, HL-60) Other: MCF7, MCF-10A, LO2, HK-2 |
||
| EZH2 (dual w/ cMyc) |
MS177 | PROTAC (CRBN) | MLL-r AML (EOL-1, MV4;11, MOLM-13, RS4;11) Other: HeLa, MM1.S, Kelly, HSPC, K562 |
Y | |
| EZH2 | E7 | PROTAC (CRBN) | NSCLC (A549, H1299) TNBC (MDA-MB-468) DLBCL (Pfeiffer, WSU-DLCL-2) Prostate (LNCaP, DU 145) Ovarian (SKOV3, A2780) |
||
| H3K36me2 | ASH1L | AS-99 | Inhibitor | Leukemia (MV4;11, MOLM13, KOPN8, K562, SET2) Other: CD34+, CD45+ |
Y |
| NSD1 | BT5 | Covalent Inhibitor | Leukemia (K562, SET2, MOLM13) Other: HEK293T, HM2, NUP98-NSD1, CD34+ |
||
| NSD2 | UNC6934 | Inhibitor | MM (KMS-11, MM1.S, UTMC2) Other: U2OS, HCT116, HEK293, HT1080, MCF7, RS4;11 |
||
| NSD2 (dual w/ IKZF1/3) | MS159 | PROTAC (CRBN) | MM (KMS11, H929) Other: 293FT |
Y | |
| NSD3 | MS9715 | PROTAC (VHL) | MLL-r AML (EOL-1, MOLM13, RS4;11) Other: MM1.S, 293FT, K562 |
||
| NSD3 | Compound 8 | PROTAC (VHL) | NSCLC (A549, NCI-H1703, H520) | Y | |
| H3K36me3 | SETD2 | EPZ-719 | Reversible Inhibitor |
MM (KMS34, KMS11) Other: A549 |
Y |
| H3K4me2 | WDR5 | Compound 8g | PROTAC (VHL) | Leukemia (MV4;11, HL-60) | |
| WDR5 | MS67 | PROTAC (VHL) |
MLL-r AML (MV4;11, EOL-1, RS4;11, THP-1, MOLM13, KOPN8) PDAC (MIA PaCa-2, HPAF-II, Panc 10.05, BxPC-3) Other: 239FT, HL-60, MCF7, NCI-H2009, PC3, SK-ES-1 |
Y | |
| WDR5 (dual w/ IKZF1/3) | MS40 | PROTAC (CRBN) |
MLL-r AML (MV4;11, RS4;11, EOL-1, KOPN8, MOLM13, THP-1) Breast (BT549, SUM149, SUM159, MCF7, T-47D, MDA-MB-231, HCC1806, WHIM12) Other: K562 |
Y | |
| H3K9me2 | G9a/GLP | MS8511 | Covalent Inhibitor | MDA-MB-231 K562 |
Y = in vivo data included