A-1155463
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) | Surpasses criterion: BCL2L1: IC50 = 0.55 nM (Time-resolved fluorescence energy transfer (TR-FRET)) |
| Selectivity within target family: goal is > 30-fold | Surpasses criterion: BCL2: IC50 = 382 nM (TR-FRET); MCL1: IC50 = 14 µM (TR-FRET) |
| Selectivity outside target family | Closest off targets at 10 µM are PPARG (99.1 % inhibition), CCKAR (98.9 %), UTS2R (94.9 %), OPRD1 (77.9 %), MAOA (74.5 %), ADORA3 (71.6 %), HRH1 (69.2 %) and PTGS2 (62.2 %) (Eurofins-Cerep screen). However, there is some indication that these are false positives due to insoluble aggregates under serum free conditions (see conclusion of profiling data).Closest off-targets in the PDSP scan are SIGMAR1 (Ki = 136.4 nM), GABA/PBR (Ki = 793.96 nM), TMEM97 (Ki = 806.12 nM), HTR3A (Ki = 1142.6 nM)KINOMEScan with 468 targets at 1 µM: Closest off-targets of primary data (% Ctrl) are AURKC (9), MARK3 (38) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Highly active in inducing apoptosis in BCL2L1 dependent cell lines, highly selective against BCL2 (RS4;11) cell lines (EC50 > 10 µM (10 % HS, 48 hr)); EC50 = 70 nM in BCL2L1 dependent H146 cells (10 % HS, 48 hr) (CTG assays) |
| Control compound (100 times less potent than the probe) | Surpasses criterion: A-1107969 >100- fold less potent in binding and cellular assays (BCL2L1: IC50 = 270 nM (TR-FRET)) |