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

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

  • J Med Chem. 2018 Aug 23;61(16):7245-7260. doi: 10.1021/acs.jmedchem.8b00664.
Shipeng He 1,  Guoqiang Dong 2,  Shanchao Wu 2,  Kun Fang 1,  Zhenyuan Miao 2,  Wei Wang 1 3,  Chunquan Sheng 2
Affiliations

Affiliations

  • 1 School of Pharmacy , East China University of Science and Technology , Shanghai 200237 , P.R. China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy , Second Military Medical University , 325 Guohe Road , Shanghai 200433 , P.R. China.
  • 3 Department of Chemistry and Chemical Biology , University of New Mexico , MSC03 2060, Albuquerque , New Mexico 87131-0001 , United States.
PMID: 30045621 DOI: 10.1021/acs.jmedchem.8b00664
Abstract

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 14d was proven to be a potent and orally active MDM2/HDAC dual inhibitor, whose antitumor mechanisms were validated in Cancer cells. Compound 14d 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.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z