FANCI Activators

FANCI activators comprise a diverse set of chemicals that exert their influence on the FANCI protein, a crucial player in DNA repair processes. These activators are strategically selected to avoid the use of traditional biological materials, proteins, and growth factors. Notably, quercetin, a flavonoid, indirectly activates FANCI by inhibiting the PI3K/Akt pathway, relieving the negative regulation imposed by this signaling cascade on FANCI. Similarly, curcumin, found in turmeric, modulates the NF-κB pathway, indirectly enhancing FANCI function by disrupting the inhibitory signals transmitted through NF-κB. Resveratrol, another FANCI activator, operates through the SIRT1/FANCI axis. By activating SIRT1, resveratrol facilitates the deacetylation of FANCI, positively influencing its stability and involvement in DNA damage response mechanisms. These examples highlight the indirect nature of FANCI activation by these chemicals, affecting upstream pathways to ultimately enhance FANCI functionality.

Moreover, inhibitors such as SB-431542 and niclosamide act on TGF-β and Wnt/β-catenin pathways, respectively, indirectly promoting FANCI activation. SB-431542 disrupts the TGF-β/FANCI regulatory axis, while niclosamide inhibits the Wnt pathway, releasing FANCI from negative regulation. These chemical interventions showcase the complexity of FANCI regulation and the diverse pathways that can be targeted to indirectly activate this pivotal protein in DNA repair. In addition, small molecules like A-443654, bortezomib, LY294002, dasatinib, trametinib, A-1210477, and selumetinib act through various mechanisms, including Akt, proteasomal degradation, PI3K, Src kinase, and MDM2, to indirectly activate FANCI. These chemicals interfere with specific signaling pathways, relieving the inhibitory constraints on FANCI and promoting its participation in maintaining genomic integrity. In summary, FANCI activators represent a spectrum of chemicals strategically chosen for their ability to modulate key cellular pathways, indirectly influencing the activation of FANCI in DNA repair processes.