@article {Wood437, author = {Dan L. Wood and Dulal Panda and Todd R. Wiernicki and Leslie Wilson and Mary Ann Jordan and Jai Pal Singh}, title = {Inhibition of Mitosis and Microtubule Function through Direct Tubulin Binding by a Novel Antiproliferative Naphthopyran LY290181}, volume = {52}, number = {3}, pages = {437--444}, year = {1997}, doi = {10.1124/mol.52.3.437}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The mechanism of action of a novel antiproliferative compound LY290181 [2-amino-4-(3-pyridyl)-4H-naphtho(1,2-b)pyran-3-carbonitrile] was characterized. LY290181 is a potent inhibitor of cell proliferation, producing 50\% inhibition of vascular smooth muscle, endothelial, Chinese hamster ovary, HeLa, and human erythroleukemia cells at concentrations of 8{\textendash}40 nm. Cell cycle analysis showed that LY290181 caused accumulation of smooth muscle cells at the G2/M phase and induced mitotic arrest in Chinese hamster ovary cells and HeLa cells. At low concentrations (3{\textendash}30 nm), LY290181 blocked transition of cells from metaphase to anaphase and disrupted mitotic spindle organization. At high concentrations (>=100 nm), LY290181 produced a concentration-dependent loss of cytoplasmic and spindle microtubules. LY290181 inhibited the polymerization of purified bovine brain microtubule protein into microtubules, and it depolymerized preformed microtubules. Using tubulin-1-anilino-8-naphthalene sulfonate complex fluorescence, we have shown that LY290181 directly interacted with tubulin in a unique manner. These studies show that LY290181 induces cell growth arrest in prometaphase/metaphase, and tubulin appears to be its molecular target.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/52/3/437}, eprint = {https://molpharm.aspetjournals.org/content/52/3/437.full.pdf}, journal = {Molecular Pharmacology} }