Biological Activity
360a is a 2,6-pyridine-dicarboxamide derivative displaying strong affinity and selectivity for g-quadruplex structures and selective telomerase inhibition in vitro assays. 360a is a g-quadruplex ligand, which can influence the consequence of g-quadruplex formation and/or stabilization.
in vitro
we found a s-phase accumulation in atm-proficient, but not in atm-deficient ebv-lymphocytes treated with 360a before induction of cell death. however, atm status did not modify cell cycle distribution in 360a-treated sv40-fibroblasts and hela cells compared to dmso treated controls [1]. dna-pkcs-dependent nhej was responsible for sister telomere fusions as a direct consequence of g-quadruplex formation and/or stabilization induced by 360a on parental telomere g strands. nhej and hr activation at telomeres altered mitotic progression in treated cells [2]. this compound was shown to display a potent affinity and selectivity for telomeric g-quadruplex dna over duplex dna and to induce delayed growth inhibition in ht1080 tumor cell line [3].
