Kinomics

Of the 517 protein kinases in the human kinome [116], structures are publicly available for < 10% of the different enzymes. In the absence of experimental data, construction of homology models based on known structures has proven a reliable method for generating 3D information. How, then, are the models built and what are the limitations of the models especially as applied to the family of protein kinases ... [Pg.53]

Vieth M, Higgs RE, Robertson DH, etal. (2004) Kinomics-structural biology and chemogenomics of kinase inhibitors and targets. Biochim. Biophys. Acta. 1697 243-257. [Pg.31]

Figure 5. An example of intra-family target hopping within kinases. According to SiteSorter, Braf kinase, the primary target for the clinical compound BAY 43-9006, is one of the 10 most similar kinases to c-Kit, which has also been shown to bind BAY 43-9006 with sub-micromolar affinity (60% of the binding site residues are consen/ed and colored blue non-consen/ed positions are colored yellow). This cross-reactivity cannot be predicted based on the sequence similarity of the Braf and c-Kit kinase domains, since approximately one-sixth of the human kinome is more sequence similar to Braf than c-KiL...

Tyner JW, Walters DK, Willis SG et al (2008) RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia. Blood 111 2238-2245... [Pg.95]

Cole KA, Huggins J, Laquaglia M et al (2011) RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHKl) as a therapeutic target in neuroblastoma. Proc Natl Acad Sci USA 108 3336-3341... [Pg.95]

Arora S, Bisanz KM, Peralta LA et al (2010) RNAi screening of the kinome identifies modulators of cisplatin response in ovarian cancer cells. Gynecol Oncol 118 220-227... [Pg.95]

SAR). In addition, small molecules have the advantage of being suitable for dose response experiments that are helpful in validating borderline hits from the kinome siRNA libraries. [Pg.103]

Knight ZA, Lin H, Shokat KM (2010) Targeting the cancer kinome through polypharmacology. Nat Rev Cancer 10 130-137... [Pg.163]

Lu Y, Muller M, Smith D et al (2010) Kinome siRNA-phosphoproteomic screen identifies networks regulating AKT signaling. Oncogene 30 4567 577... [Pg.213]

Tiedemann RE, Zhu YX, Schmidt J et al (2010) Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase, GRK6. Blood 115 1594-1604... [Pg.322]

Patricelli MP, Szardenings AK, Liyanage M et al (2007) Functional interrogation of the kinome using nucleotide acyl phosphates. Biochemistry 46 350-358... [Pg.39]

Doerig C, Abdi A, Bland N et al (2010) Malaria targeting parasite and host cell kinomes. Biochim Biophys Acta 1804(3) 604-612... [Pg.225]

Doerig C, Billker O, Pratt D, Endicott J (2005) Protein kinases as targets for antima-larial intervention kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes. Biochim Biophys Acta 1754(1-2) 132-150... [Pg.225]

Plasmodium falciparum the kinome of a divergent eukaryote. BMC Genomics 5 79... [Pg.225]

Anamika K, Srinivasan N (2007) Comparative kinomics of Plasmodium organisms unity in diversity. Protein Pept Lett 14(6) 509-517... [Pg.225]

Kannan N, Taylor SS, Zhai YF, Venter JC, Manning G (2007) Structural and functional diversity of the microbial kinome. PLoS Biol 5 467 -78... [Pg.129]

Chemical Kinomics A Target Gene Family Approach in Chemical Biology 1169... [Pg.169]

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