title: Protein Complex Production from the Drug Discovery Standpoint.
abstract: Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.
authors.affiliation: Crelux GmbH, Am Klopferspitz 19a, D82152, Martinsried, Germany. moarefi@crelux.com.
authors.forename: Ismail
authors.initials: I
authors.lastname: Moarefi
mesh_terms: D000818:Animals; D001681:Biological Assay; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes; D015202:Protein Engineering / Q000379:methods*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D004791:Enzyme Inhibitors; D046912:Multiprotein Complexes; D021122:Protein Subunits; D011994:Recombinant Proteins
keywords: Protein complex expression; Protein complexes; Proteomics; Small molecule drug discovery; Structure based drug discovery