title: Progress towards the development of SH2 domain inhibitors.
abstract: Src homology 2 (SH2) domains are 100 amino acid modular units, which recognize and bind to tyrosyl-phosphorylated peptide sequences on their target proteins, and thereby mediate intracellular protein-protein interactions. This review summarizes the progress towards the development of synthetic agents that disrupt the function of the SH2 domains in different proteins as well as the clinical relevance of targeting a specific SH2 domain. Since 1986, SH2 domains have been identified in over 110 human proteins, including kinases, transcription factors, and adaptor proteins. A number of these proteins are over-activated in many diseases, including cancer, and their function is highly dependent on their SH2 domain. Thus, inhibition of a protein's function through disrupting that of its SH2 domain has emerged as a promising approach towards the development of novel therapeutic modalities. Although targeting the SH2 domain is a challenging task in molecular recognition, the progress reported here demonstrates the feasibility of such an approach.
authors: Department of Chemical and Physical Sciences, University of Toronto, 3359 Mississauga Road North, Mississauga, Ontario L5L 1C6, Canada.
authors: Dziyana
authors: D
authors: Kraskouskaya
authors: Eugenia
authors: E
authors: Duodu
authors: Carolynn C
authors: CC
authors: Arpin
authors: Patrick T
authors: PT
authors: Gunning
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D051380:GRB2 Adaptor Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D051382:GRB7 Adaptor Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D050796:STAT3 Transcription Factor; D054852:Small Molecule Libraries; D014157:Transcription Factors; D051382:GRB7 Adaptor Protein; D011505:Protein-Tyrosine Kinases