Small Molecules Simultaneously Inhibiting p53-Murine Double Minute 2 (MDM2) Interaction and Histone Deacetylases (HDACs): Discovery of Novel Multitargeting Antitumor Agents

Published on 2018-08-09T19:05:02Z (GMT) by
p53-Murine double minute 2 (MDM2) interaction and histone deacetylases (HDACs) are important targets in antitumor drug development. Inspired by the synergistic effects between MDM2 and HDACs, the first MDM2/HDACs dual inhibitors were identified, which showed excellent activities against both targets. In particular, compound <b>14d</b> was proven to be a potent and orally active MDM2/HDAC dual inhibitor, whose antitumor mechanisms were validated in cancer cells. Compound <b>14d</b> showed excellent in vivo antitumor potency in the A549 xenograft model, providing a promising lead compound for the development of novel antitumor agents. Also, this proof-of-concept study offers a novel and efficient strategy for multitargeting antitumor drug discovery.

Cite this collection

He, Shipeng; Dong, Guoqiang; Wu, Shanchao; Fang, Kun; Miao, Zhenyuan; Wang, Wei; et al. (2018): Small Molecules

Simultaneously Inhibiting p53-Murine Double Minute 2 (MDM2) Interaction

and Histone Deacetylases (HDACs): Discovery of Novel Multitargeting

Antitumor Agents. ACS Publications. Collection.