A-485
Probe criteria
| Inhibitor/agonist potency: goal is < 50 nM (IC50, KD) | Surpasses criterion: EP300 (BHC): IC50 = 10 nM (TR-FRET); EP300 (HAT): KD = 15 nM (SPR); CREBBP (BHC): IC50 = 3 nM (TR-FRET) |
| Selectivity within target family: > 30-fold | Surpasses criterion: Cellular selectivity demonstrated - inhibits H3K27 but not H3K9 acetylationSelective against other available HATs (MYST3, MYST4, PCAF, HAT1, TIP60 and GCN5L2) |
| Selectivity outside target family | Selective against BRDs (BRD3, BRD4, BRDT), Kinases (78) and common targets (CEREP) except for the dopamine and serotonin transporter (< 90 % inhibition). SLC6A3 (Ki= 1817.04 nM) and SLC6A4 (Ki= 223.27 nM) activity was also found in the PDSP scan. Other hits in the PDSP scan are GABA/PBR (Ki= 1107.62 nM) and HTR2B (Ki= 1292.04 nM) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: IC50 = 150 nM in inhibition of H3K27Ac |
| Control compound (100 times less potent than the probe) | Surpasses criterion: In vitro: >1000-fold less potent; Shows off-target activity in the PDSP scan: the closest hits are DRD3 (Ki = 1136.58 nM) and GABA/PBR (Ki= 2577.3 nM) |