Nutlin-3 is a small-molecule inhibitor of MDM2 (mouse double minute 2) with IC50 value of 0.09μM [1].
Nutlin-3 binds MDM2 in the TP53-bindingpocket, thereby interfering with MDM2-directed TP53 degradation. This has been shown to cause cell cycle arrest, growth inhibitionand apoptosis in both solid tumors and lymphoid neoplasms.In mantle cell lymphoma(MCL), it is reported that Nutlin-3 can inhibit cell growth and activate apoptosis in bothwt-TP53(IC50 of 1 to 10μM) and mt-TP53(IC50 of 22.5μM) cells [2].
Nutlin-3 can also effectcell cycle in gastric cancer cell lines. It induces G1 arrest inMKN-45 and SNU-1 cell lines. In vitro assay shows Nutlin-3can enhance the antitumoreffects of conventional chemotherapeutic agents in several gastric cancer cell lines. And in in vivo assay, Nutlin-3 significantly inhibits the growth of xenograft tumors [3].
References:
[1] Lyubomir T.Vassilev et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.Science.2004, 303: 844-848.
[2] Yoko Tabe, Denise Sebasigari, Linhua Jin, et al.MDM2 Antagonist Nutlin-3 Displays Antiproliferative andProapoptotic Activity in Mantle Cell Lymphoma. Clin Cancer Res. 2009, 15:933-942.
[3] Shinji Endo,Kenji Yamato,Sachiko Hirai,Toshikazu Moriwaki,Kuniaki Fukuda,Hideo Suzuki,Masato Abei,Ichiro Nakagawa and IchinosukeHyodo.Potent in vitro and in vivo antitumor effects ofMDM2 inhibitor nutlin-3 in gastric cancer cells.Cancer Science. 2011, 102 (3): 605-613.
