Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Cancer

Mdm2 p53 binding protein homolog (MDM2; HDM2); p53

SAR studies identified a series of MDM2-p53 interaction inhibitors that could be useful for treating cancer. In the first study, in vitro assays identified piperidone compounds that bound the N-terminal tail of MDM2 and stabilized the protein's structure, and decreased p53 binding compared with vehicle. In the second study, cell culture and mouse studies identified orally available, high-affinity pyrrolidone inhibitors of the MDM2-p53 interaction that decreased tumor growth more effectively than a reference compound. Next steps include further lead optimization and selection of preclinical candidates from both series.

SciBX 5(42); doi:10.1038/scibx.2012.1104
Published online Oct. 25, 2012

Findings in first study covered by pending patent; licensing status undisclosed

Findings in second study covered by pending patent; available for licensing

Michelsen, K. et al. J. Med. Chem.; published online Sept. 19, 2012;
doi:10.1021/ja305839b
Contact: Leszek Poppe, Amgen Inc., Thousand Oaks, Calif.
e-mail:

lpoppe@amgen.com
Contact: Xin Huang, same affiliation as above
e-mail:

hxin@amgen.com

Zhuang, C. et al. J. Med. Chem.; published online Oct. 9, 2012;
doi:10.1021/jm300969t
Contact: Wannian Zhang, Second Military Medical University, Shanghai, China
e-mail:

zhangwnk@hotmail.com
Contact: Chunquan Sheng, same affiliation as above
e-mail:

shengcq@hotmail.com