Small molecule inhibitors of the class 1 receptor tyrosine kinase family.
This review covers literature describing research progress in erbB family tyrosine kinase inhibition over the last year. Excellent recent reviews are available, thus we have focussed on current developments of leading small molecule drug candidates as well as their erbB family inhibition profile. The most advanced erbB family tyrosine kinase (TK) inhibitors are demonstrating promising anti-cancer activity in clinical trials and are discussed. Several inhibition strategies are emerging: EGFR TK selective, irreversible TK inhibition and dual EGFR/erbB2 TK inhibitors. While small structural differences are seen in the leading compounds, the variations in their inhibition profiles and compound properties suggest that biological systems judge structural diversity differently. The readers' attention is drawn to common issues of selectivity and potency generally encountered with kinase inhibitors.
Cockerill
G Stuart
GS
Drug Discovery, Arrow Therapeutics, Britannia House, 7 Trinity Street, London. SE1 1DS UK and GlaxoSmithKline, Discovery Research Kinase Chemistry, 5 Moore Dr, Research Triangle Park, NC 27709, USA. jacques.dumas.b@bayer.com
Lackey
Karen E
KE
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000145:classification / Q000201:enzymology; D018739:Oncogene Proteins v-erbB / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018739:Oncogene Proteins v-erbB; D011799:Quinazolines; D020794:Receptor Protein-Tyrosine Kinases