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The NF-κB Inhibitor Pyrrolidinedithiocarbamate Ammonium (PDTC) Exerts an Anti-Pyroptotic Effect in Monocytes
Xianxian Mao1,2, Yihan Wang3, Hongru Lin3,4
1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, PR China.
Current Medicinal Chemistry
|July 16, 2026
Summary
Pyrrolidinedithiocarbamate ammonium (PDTC) effectively inhibits pyroptosis, a form of inflammatory cell death, in monocytes. PDTC works by suppressing the NF-κB pathway and regulating NLRP3 expression, offering potential for treating inflammatory diseases.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Pyroptosis is inflammatory programmed cell death triggered by inflammasomes.
- It exacerbates inflammation and disease progression, but effective interventions are lacking.
Purpose of the Study:
- Screen small-molecule inhibitors for anti-pyroptotic activity in monocytes.
- Elucidate the mechanism of the most potent inhibitor.
Main Methods:
- Used human monocytic leukemia THP-1 cells stimulated with LPS and nigericin.
- Screened 14 small molecules, assessing cell viability (CCK-8) and cytotoxicity (LDH release).
- Analyzed pyroptosis pathway proteins (Western blotting) and NLRP3 mRNA (qPCR), exploring regulatory mechanisms with proteasomal and lysosomal inhibitors.
Main Results:
- Pyrrolidinedithiocarbamate ammonium (PDTC), an NF-κB inhibitor, showed significant anti-pyroptotic effects.
- PDTC reduced LDH release, improved cell viability, and suppressed canonical pyroptosis pathway activation by downregulating NLRP3, caspase-1, GSDMD cleavage, and IL-1β secretion.
- PDTC inhibited NF-κB signaling and regulated NLRP3 via proteasomal degradation and transcriptional suppression.
Conclusions:
- PDTC is a potent monocyte pyroptosis inhibitor, acting via NF-κB suppression and dual NLRP3 regulation.
- Its mechanism extends beyond NF-κB inhibition, with distinct optimal concentrations for NF-κB inhibition and anti-pyroptosis.
- PDTC demonstrates therapeutic potential for inflammatory disorders.
