abexinostat + exatecan

Abexinostat + exatecan is a pharmacological combination consisting of abexinostat, an orally bioavailable pan-histone deacetylase (HDAC) inhibitor, and exatecan, a synthetic camptothecin derivative that acts as a DNA topoisomerase I inhibitor. Abexinostat inhibits HDAC enzymes (primarily HDAC1, HDAC2, HDAC3, HDAC6, and HDAC10), leading to hyperacetylation of histones, chromatin remodeling, and transcription of tumor suppressor genes, while also downregulating the DNA repair protein RAD51. Exatecan binds to and stabilizes the topoisomerase I-DNA cleavable complex, preventing DNA ligation and inducing lethal double-strand DNA breaks during replication. The combination of these two mechanisms is studied for potential synergistic antineoplastic activity, as HDAC inhibition-mediated chromatin relaxation and DNA repair impairment can sensitize cancer cells to topoisomerase I inhibitor-induced DNA damage.

Other names

PCI-24781 + DX-8951fabexinostat + exatecan