Table 1 Main direct inhibitors of G9a HMTase activity reported in the literature.
From: Emerging role of G9a in cancer stemness and promises as a therapeutic target
Compound name | Structure | Class of inhibitor | Selectivity, [Ref.] | Notable anticancer effects, [Ref.] | In vivo tested, [Ref.] | Clinical development status | Reported limitations to clinical development, [Ref.] |
|---|---|---|---|---|---|---|---|
BIX-01294 | Quinazoline core | H3 peptide competitive | G9a (2.7 uM) > GLP (38 uM), [92] | Yes, [108] | Experimental | ||
UNC0638 | Quinazoline core | H3 peptide competitive | G9a (<15 nM) > GLP (19 nM), [93] | Yes, [99] | Experimental | Poor in vivo pharmacokinetic (PK) properties, [95] | |
UNC0642 | Quinazoline core | H3 peptide competitive | G9a = GLP (<2.5 nM), [94] | Yes, [89] | Experimental | Toxicity in normal plasma cells, [103] | |
A-366 | Indole core | Non-SAM competitive | G9a (3.3 nM) >GLP (38 nM), [95] | Yes, [96] | Preclinical (Leukemia) | Unknown | |
CM-272 | Quinoline core/Dual | H3 + DNA substrate competitive | G9a (8 nM) >DNMT1 (382 nM), [95] | Preclinical (Hematopoietic malignancies, bladder) | Unknown | ||
DS79932728 | Aminoindole core | Non-SAM competitive | G9a (12.6 nM) >GLP (75.7 nM), [101] | No | Yes, [101] | Preclinical (β-thalassemia and sickle cell disease) | Unknown |
EZM-8266 | Unknown | Unknown | Unknown | No | Yes, [Unpublished, Epizyme, Inc] | Preclinical (Sickle cell disease) | Discontinued due to preclinical toxicology concerns [101] |
