A Probe for NLRP3 Inflammasome Inhibitor MCC950 Identifies Carbonic Anhydrase 2 as a Novel Target
Cassandra R. Kennedy, Andrea Goya Grocin, Tristan Kovačič, Ravi Singh, Jennifer Ward, Avinash R. Shenoy, Edward W. Tate
Abstract
, and independent cellular thermal proteomic profiling revealed stabilization of CA2 by MCC950. MCC950 displayed noncompetitive inhibition of CA2 activity, confirming carbonic anhydrase as an off-target class for this compound. These data highlight potential biological mechanisms through which MCC950 and derivatives may exhibit off-target effects in preclinical or clinical studies.
Topics & Concepts
InflammasomeCarbonic anhydraseChemistryReceptorBiochemistryEnzymeCell biologyBiologyInflammasome and immune disordersAdenosine and Purinergic SignalingHeme Oxygenase-1 and Carbon Monoxide