Table 1.
Small molecule inhibitors targeting NLRP3 inflammasome signaling.
| Targets | Agents | Description |
|---|---|---|
| NLRP3 | Direct | |
| MCC950 (CP-456773) | Binds to walker B motif of NACHT domain and locks inactive conformation | |
| RRx-001 | Covalently binds to cysteine 409 of NLRP3 | |
| CY-09 | Binds to walker A motif of NACHT domain and inhibits ATPase activity | |
| Compound 6 | Directly binds to the NACHT domain of NLRP3 to inhibit NLRP3 ATPase activity | |
| OLT1177 | Covalently modifies NACHT domain to inhibits its ATPase activity | |
| MNS | Directly binds to NLRP3, inhibits ATPase activity and prevents NLRP3-ASC interaction | |
| BOT-4-one | Leads to NLRP3 alkylation, inhibits ATPase activity of NLRP3 | |
| INF39 | Inhibits ATPase activity of NLRP3; inhibits priming | |
| Fluoxetine | Inhibits activation of the NLRP3-ASC inflammasome | |
| Indirect | ||
| Thiolutin (THL) | Inhibits NLRP3 deubiquitination and activation | |
| dihydrotanshinone I (DHT) | Inhibits ASC oligomerization induced by NLRP3 agonists | |
| methyl gallate | Blocks the ROS over-generation and oligomerization of NLRP3 | |
| IL-1β | Canakinumab | Neutralization IL-1β antibody |
| Anakinra | IL-1β receptor antagonist | |
| Rilonacept | Neutralizes circulating IL-1β and IL-1α | |
| P2X7 | AZ10606120 | P2X7R antagonist |
| Avastin | P2X7R inhibitor | |
| AZD9056 | P2X7R inhibitor | |
| Glyburide | Broad-spectrum inhibitor of P2X7R | |
| Caspase-1 | Ritonavir | Specific caspase-1 inhibitor |
| Disulfiram | Specific caspase-1 inhibitor | |
| Ac-YVAD-CHO | Caspase-1 inhibitory peptide | |
| VX-740/765 | Caspase-1 inhibitor | |
| Pralnacasan (VX-740) | Caspase-1 inhibitor | |
| Ac-FLTD-CMK | Inflammatory caspases inhibitor, targets caspases-1, -4, -5, and -11 | |
| Tetracycline | Unknown | |
| ASC | MM01 | Prevents ASC speck formation |
| IC100 | Humanized antibody targeting ASC | |
| ROS | N-acetyl Cysteine (NAC) | ROS generation inhibitor |
| NF-κB | BAY-11-7082 | NF-κB inihibitor |
| GSDMD | dimethyl fumarate (DMF) | Reacts with GSDMD and prevents its capacity to induce cell death |