MDM2-p53 interaction inhibitors Library
ChemDiv’s MDM2-p53 Interaction Inhibitors Library contains 22,319 compounds.
ChemDiv proposes the new library of drug-like MDM2-p53 interaction inhibitors; this library represents a selection of drug-like compounds aimed at modulating protein-protein interaction (PPI) of MDM2 with protein p53 involved in tumorogenesis. The library has been assembled using ChemDiv’s in house structural biology insight, molecular stimulation-modeling, and virtual screening of ChemDiv’s novel chemistries and medicinal chemistry filtering/ranking of the resulting hits. A representative example of a ‘druggable’ ‘hot spot’ included specific topological features of the MDM2-p53 interaction. For example, the cocrystal structure reveals that three amino acid residues of p53 (Trp23, Leu26, and Phe19) are responsible for key hydrophobic contacts with the MDM2 protein. Furthermore, the cocrystal structures of known small molecules bound to MDM2 support the importance of targeting these three hydrophobic regions when attempting to disrupt the MDM2−p53 PPI.
ChemDiv combined a number of in silico screening approaches and specific spatial PPI information to design sub-libraries centered on a scaffolds that project side chain functionalities with distance and angular properties similar to those seen in the MDM2 interacting motif of p53.
ChemDiv proposes the new library of drug-like MDM2-p53 interaction inhibitors; this library represents a selection of drug-like compounds aimed at modulating protein-protein interaction (PPI) of MDM2 with protein p53 involved in tumorogenesis. The library has been assembled using ChemDiv’s in house structural biology insight, molecular stimulation-modeling, and virtual screening of ChemDiv’s novel chemistries and medicinal chemistry filtering/ranking of the resulting hits. A representative example of a ‘druggable’ ‘hot spot’ included specific topological features of the MDM2-p53 interaction. For example, the cocrystal structure reveals that three amino acid residues of p53 (Trp23, Leu26, and Phe19) are responsible for key hydrophobic contacts with the MDM2 protein. Furthermore, the cocrystal structures of known small molecules bound to MDM2 support the importance of targeting these three hydrophobic regions when attempting to disrupt the MDM2−p53 PPI.
ChemDiv combined a number of in silico screening approaches and specific spatial PPI information to design sub-libraries centered on a scaffolds that project side chain functionalities with distance and angular properties similar to those seen in the MDM2 interacting motif of p53.