公开(公告)号：US20150246946A1

公开(公告)日：2015-09-03

申请号：US14432729

申请日：2013-10-01

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Thomas Leonard Joseph ,  Chandra Shekhar Verma ,  David Phillip Lane ,  Christopher John Brown

IPC: C07K7/06 ,  A61K38/08

CPC classification number: C07K7/06 ,  A61K38/00 ,  A61K38/08 ,  A61K38/10 ,  A61K45/06 ,  C07K7/08 ,  A61K2300/00

Abstract: By using a phage display derived peptide as an initial template, compounds have been developed that are highly specific against Mdm2/Mdm4. These compounds exhibit greater potency in p53 activation and protein-protein interaction assays than a compound derived from the p53 wild-type sequence. Unlike nutlin, a small molecule inhibitor of Mdm2/Mdm4, the phage derived compounds can arrest cells resistant to p53 induced apoptosis over a wide concentration range without cellular toxicity, suggesting they are highly suitable for cyclotherapy.

Abstract translation: 通过使用噬菌体展示衍生肽作为初始模板，开发了对Mdm2 / Mdm4具有高度特异性的化合物。 与来自p53野生型序列的化合物相比，这些化合物在p53活化和蛋白质 - 蛋白质相互作用测定中表现出更大的效力。 与Mdm2 / Mdm4的小分子抑制剂nutlin不同，噬菌体衍生的化合物可以在宽的浓度范围内阻止对p53诱导的细胞凋亡的细胞，而无细胞毒性，表明它们非常适合于环境疗法。