NVS-MALT1
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) | Surpasses criterion: Human biochemical (TR-FRET) assay: MALT1 IC50 = 18 nM (low salt) and 2.4 nM (high salt) |
| Selectivity within target family: > 30-fold | Surpasses criterion: No cross reactivity among proteases owing to allosteric mechanism. |
| Selectivity outside target family | Surpasses criterion: No activities across a panel of 50 kinases at 10 µM (except for FLT3 with 3.5 µM inhibition). No activities across a panel of 110 receptors, ion channels, enzymes and transporters at 10 µM (except for 52% inhibition of adenosine transporter AdT).Clean PDSP scan |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: Jurkat IL-2 (IL2-RGA PMA + anti-CD28): IC50 = 3.4 nM; IL-2 – PMA + anti-CD28 + 50% Human whole blood IC50 = 200 nM; IL-2 – PMA + anti-CD28 + 50% Rat whole blood IC50 = 130 nM |
| Control compound (100 times less potent than the probe) | NVS-MALT1-C: Human biochemical (TR-FRET) assay: MALT1 IC50 = 190 nM (high salt); Jurkat IL-2 (IL2-RGA PMA + anti-CD28): IC50 = 1.9 µM Only off-targets in the PDSP scan (43 targets) at 10 µM are TMEM97 (Ki = 889.82 nM) and SIGMAR1 (Ki = 1593.68 nM) |