Adenosine-anchored triphosphate subsite probing: distinguishing between HER-2 and HER-4 tyrosine protein kinases.
A strategy of full-site occupancy and stereospecific recognition in the triphosphate subsite was used to specifically inhibit two protein kinases HER-2 and HER-4 from the EGFR family. The SAR profiles of a panel of adenosine-anchored bicyclic heterocycles against HER-2 and HER-4 indicated that specificity can be derived for highly homologous protein kinases from stereospecific recognition in the triphosphate-subsite.
D000241:Adenosine / Q000737:chemistry*; D001549:Benzamides; D004791:Enzyme Inhibitors / Q000737:chemistry; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000068877:Imatinib Mesylate; D008958:Models, Molecular; D015335:Molecular Probes; D010710:Phosphates / Q000737:chemistry*; D010879:Piperazines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D066247:Receptor, ErbB-4; D013329:Structure-Activity Relationship
D000241:Adenosine; D001549:Benzamides; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D000068877:Imatinib Mesylate; D015335:Molecular Probes; D010710:Phosphates; D010879:Piperazines; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4