6-Chloro-1,5-dihydro-7-(4-methylphenyl)imidazo[2,1-b]quinazolin-2(3H)-one

Uses

Antitumor agent-100 (compound A6) is an orally available apoptosis inducer and molecular gel targeting PDE3A-SLFN12 (IC50: 0.3 μM) with antitumor activity. Antitumor agent-100 binds to the PDE3A enzyme pocket to recruit and stabilize SLFN12, thereby preventing protein translation and leading to apoptosis[1].

Biological Activity

Anagrelide analog A6 is a cell penetrant and potent apoptosis inducer th at works as a molecular glue bringing together phosphodiesterase 3A (PDE3A) and Schlafen 12 protein (SLFN12) forming heterotetrametric complex. Apparently, anagrelide analog A6 binds to the PDE3A enzymatic pocket th at allows recruitment and stabilization of SLFN12, which in turn blocks protein translation, leads to apoptosis. It exhibits potent anticancer activity in cell cultures and in a tumor xenograft model.

References

[1] Jie Chen, et al. Structure of PDE3A-SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells. Nat Commun. 2021 Oct 27;12(1):6204. DOI:10.1038/s41467-021-26546-8