Chemical inhibitors of CCDC22 operate through various mechanisms to impede the protein's function within cellular processes. For instance, WZ4003 targets NUAK family kinase 1 (NUAK1), a kinase that plays a pivotal role in cellular adhesion processes. By inhibiting NUAK1, WZ4003 indirectly hampers the regulatory influence of CCDC22 on cellular adhesion and migration. Similarly, GSK690693 acts by inhibiting AKT, a kinase that phosphorylates substrates within the NF-kB signaling pathway, where CCDC22 is also known to operate. The inhibition of AKT by GSK690693, therefore, can reduce the phosphorylation of substrates in this pathway, which in turn diminishes the regulatory role of CCDC22. MLN4924 takes a different approach by targeting the NEDD8 activating enzyme, which is responsible for the neddylation that modifies proteins engaged in the NF-kB pathway. By inhibiting this enzyme, MLN4924 can decrease the neddylation-dependent modulation of components within the NF-kB pathway, affecting the functionality of CCDC22.
Additional chemicals further elucidate the multifaceted approach to inhibiting CCDC22. PF-4708671 focuses on p70 S6 Kinase, integral to protein synthesis and cell growth. By inhibiting this kinase, PF-4708671 can reduce the processes that CCDC22 is thought to influence. The compounds Torin 1 and INK128 both target mechanistic target of rapamycin (mTOR) in different complexes, mTORC1 and mTORC1/2 respectively. Inhibition of these complexes interferes with cellular growth and autophagy, processes in which CCDC22 has been implicated. BMS-345541 specifically inhibits IKK, thus blocking the activation of the NF-kB pathway and consequently affecting the role of CCDC22. AZD8055, on the other hand, broadly inhibits both mTORC1 and mTORC2, disrupting their control over cell growth and survival, which in turn influences the action of CCDC22. Likewise, PF-04691502 and Palomid 529 target both PI3K and mTOR or the AKT/mTOR pathway, respectively, which are involved in signaling pathways that regulate cell growth and survival, thereby affecting the function of CCDC22. Lastly, CCT128930 and PP242 inhibit AKT and mTOR kinase activity, respectively, affecting survival pathways and signaling that control cell growth, metabolism, and autophagy, where CCDC22 may be implicated, resulting in the reduced functionality of this protein.
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