Wednesday, 29 March 2023 to Thursday, 30 March 2023

A Novel Molecular Degrader for the Regulation of the NF-κB Pathway for Non-small Cell Lung Cancer Treatment.


F Hammoud1; GG Rigana1; BM Samudio2; LJ Byrne1; CM Wilson1
1 Canterbury Christ Church University, UK;  2 Atomwise, United States


Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality globally. The NF-κB pathway has been found to be crucial in cancer signaling and its inhibition has been proposed as a potential treatment. Compound 29 is an AI designed compound which acts as a molecular glue degrader, targeting the degradation of p65 protein which is associated with the NF-κB signalling pathway. Herein, we aim to investigate 1) the anti-proliferative and migratory properties of the proposed compound with relation to sortilin and 2) the regulation of the NF-κB signalling cascade. Our results supported that compound 29 sufficiently slowed down the proliferation and the migration of NSCLC, and efficiently inhibited the NF-kB pathway. Interestingly, the regulation of sortilin enhanced cellular death and the delay of cell metastasis. To conclude, the novel compound exhibited inhibitory and anti-cancer properties thus making it a promising therapeutic strategy for cancers upregulating the NF-kB pathway.

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