Kinase inhibitors ligands

Structure-based design has been employed in some powerful examples of chemical genetics by teams led by Kevan Shokat and by John Koh. Shokat s team has studied the function of kinases by engineering designed modifications into both the kinase and kinase inhibitor ligand to create highly selective chemical tools that can then be used to probe the function of individual kinases in complex kinase cascades (for an explanation of the basic concept see Figure 3.6) [20],... 

Poly(ADP-ribose)polyrmerase (PARP) inhibitors, 42 (2004) 125 P2 Purinoreceptor ligands, 38 (2001) 115 p38 MAP kinase inhibitors, 38 (2001) 1 Paclitaxel, anticancer agent, 32 (1995) 289... 

Figure 11. Potent tyrosine kinase inhibitors discovered through Combinatorial Target-Guided Ligand Assembly.

Pierce, A.C., Sandretto, K.L., and Bemis, G.W. Kinase inhibitors and the case for CH... O hydrogen bonds in protein-ligand binding. Proteins Struc., Func., Genet. 2002, 49, 567—576. 

Table 3.2 IC50 values and protein-ligand dissociation half-lives for a proprietary series of Zap-70 Kinase inhibitors.

Key words PGVL Hub, combinatorial chemistry, library design, reaction, synthesis protocol, reactant, product, enumeration, filtering, Chkl, kinase, inhibitor, SAR, ADME T (Adsorption, Distribution, Metabolism, Excretion, and Toxicity), selectivity, solubility, protein-ligand complex. 

Aronov, A. M. and Bemis, G. W., A minimalist approach to fragment-based ligand design using common rings and linkers application to kinase inhibitors. Proteins, 2004, 57, 36-50. 

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