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A Re‐examination of the MDM2/p53 Interaction Leads to Revised Design Criteria for Novel Inhibitors
Author(s) -
Vasilevich Natalya I.,
Afanasyev Ilya I.,
Kovalskiy Dmitry A.,
Genis Dmitry V.,
Kochubey Valery S.
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12351
Subject(s) - protein data bank (rcsb pdb) , computational biology , scaffold , epitope , chemistry , protein–protein interaction , molecular model , combinatorial chemistry , biochemistry , computer science , database , biology , antibody , genetics
The general model of epitope‐type MDM 2 inhibitor was developed based on the structural information on the complexes between MDM 2 and various low molecular weight ligands found in the PDB database. Application of this model to our in‐house library has led us to a new scaffold capable of interrupting protein–protein interactions. A synthetic library based on this and related scaffolds resulted in new classes of compounds that possess biochemical and cellular activity and good pharmacokinetic properties. We assume that such general approach to PPI inhibitors design may be useful for the development of inhibitors of various PPI types, including Bcl/ XL .