JNJ-79883960
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | Surpasses criterion: Target Engagement achieved with: Nano-DSF, HDx – Hydrogen / Deuterium exchange, ATPase activity, Cryo-EM generated <3Å |
| Selectivity within target family: > 30-fold | Tested some of the other 11 human inflammasomes: A panel of inflammasome triggers was used to look at inhibition (with 10 µM of JNJ-79883960) of the NLRP3, NLRC4, Pyrin, AIM2 and NLRP1b inflammasome. Highly selective for the NLRP3 inflammasome. |
| Selectivity outside target family | All analogs were clean in CEREP and DiscoverX kinase panel |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: NLRP-3 cell assay: NLRP3 PBMC IL1β: IC50 = 27.6 nM; NLRP3 PBMC IL6: IC50 > 10 µM; NLRP3 PBMC TNFα: IC50 > 10 µM |
| Control compound (100 times less potent than the probe) | JNJ-78832000: NLRP3 PBMC IL1β: IC50 < 20 µM; NLRP3 PBMC IL6: IC50 > 20 µM; NLRP3 PBMC TNFα: IC50 > 20 µM |