In vitro activity: Remodelin, via inhibition of NAT10, mediates nuclear shape rescue of LMNA depleted cells by microtubule reorganization, and improves nuclear shape and fitness of HGPS cells. Remodelin may thus provide opportunities for alleviating dystrophic and premature-ageing diseases.

Kinase Assay: Remodelin is a novel and potent acetyl-transferase NAT10 inhibitor that is cell-permeable and stable analog of CPTH2. Remodelin inhibits acetyl-transferase NAT10, a nucleolar N-acetyltransferase involved in stabilization of microtubules. Remodelin was found to correct cell defects associated with progeria, restoring and improving nuclear shape and reducing the DNA damage believed to be associated with mutations in the gene for laminin A. Remodelin can improve nuclear architecture, chromatin organization, and fitness of both human lamin A/C-depleted cells and HGPS-derived patient cells, and decrease markers of DNA damage in these cells. Remodelin is a useful chemical tool to study how NAT10 affects nuclear architecture and suggest alternative strategies for treating laminopathies and aging.

Cell Assay: In U2OS cells and normal fibroblasts, remodelin inhibited nuclear shape defects induced by farnesyltransferase inhibitors (FTI). In HGPS cells, remodelin reduced the amount of misshapen nuclei, suggesting that inhibition of NAT10 mediated nuclear shape normalization. Also, remodelin reduced DNA damage signaling, reduced SUN1 accumulation at the nuclear envelope, reduced the levels of autophosphorylated ATM and DNA double-strand break markers γH2AX, and improved chromatin and nucleolar organization. In siLMNA and HGPS cells, remodelin inhibited microtubule anchorage to centrosomes.