Chemical inhibitors of CARD 8 include a range of compounds that target the NF-kB signaling pathway, which is upstream of CARD 8's role in inflammasome assembly and activation. Parthenolide acts to impede the inflammatory cascade by blocking the IκB kinase complex, thereby preventing the activation of CARD 8 within inflammasomes. Similarly, Bay 11-7082 irreversibly inhibits the phosphorylation of IκBα, which is necessary for the activation of NF-kB and subsequently reduces CARD 8 activity. Sulforaphane also targets this pathway by preventing the degradation of IκBα, maintaining the repression of NF-kB and thus CARD 8's inflammasome activity. Disulfiram contributes to this cascade by reducing NF-kB pathway activity, which in turn would diminish CARD 8's functional role in inflammasome formation. MG132, as a proteasome inhibitor, stabilizes IκBα and decreases the activity of NF-kB, leading to a functional inhibition of CARD 8.
Continuing with the theme of NF-kB pathway inhibition, QNZ, also known as EVP4593, prevents the nuclear translocation of the NF-kB subunit p65, thereby curtailing CARD 8 activation. PDTC follows suit by obstructing NF-kB signaling, which is essential for the activation of CARD 8 in inflammasomes. Andrographolide, through its inhibitory effect on NF-kB activation, impedes the functionality of CARD 8 in inflammasome assembly. Triptolide's inhibition of the NF-kB pathway reduces the expression of pro-inflammatory cytokines and the activation of downstream proteins like CARD 8. Capsazepine blocks NF-kB pathway activation, crucial for CARD 8 function within the inflammasome complex. Isoliquiritigenin prevents the phosphorylation and degradation of IκBα, leading to CARD 8 inhibition. Lastly, curcumin is known for its capacity to inhibit the NF-kB pathway, consequently downregulating the activation of CARD 8 involved in inflammatory responses.
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