6LS4
A novel anti-tumor agent S-40 in complex with tubulin
6LS4 の概要
| エントリーDOI | 10.2210/pdb6ls4/pdb |
| 分子名称 | Tubulin alpha-1B chain, Tubulin beta chain, Stathmin, ... (10 entities in total) |
| 機能のキーワード | mitosis, antitumor protein, structural protein |
| 由来する生物種 | Sus scrofa (Pig) 詳細 |
| タンパク質・核酸の鎖数 | 5 |
| 化学式量合計 | 221758.00 |
| 構造登録者 | |
| 主引用文献 | Du, T.,Lin, S.,Ji, M.,Xue, N.,Liu, Y.,Zhang, Z.,Zhang, K.,Zhang, J.,Zhang, Y.,Wang, Q.,Sheng, L.,Li, Y.,Lu, D.,Chen, X.,Xu, H. A novel orally active microtubule destabilizing agent S-40 targets the colchicine-binding site and shows potent antitumor activity. Cancer Lett., 495:22-32, 2020 Cited by PubMed Abstract: The tubulin colchicine binding site has been recognized as an attractive drug target to combat cancer, but none of the candidate drugs have been approved for medical treatment. We recently identified a structurally distinct small molecule S-40 as an oral potent tubulin destabilizing agent. Crystal structure analysis of S-40 in a complex with tubulin at a resolution of 2.4 Å indicated that S-40 occupies all 3 zones in the colchicine pocket with interactions different from known microtubule inhibitors, presenting unique effects on assembly and curvature of tubulin dimers. S-40 overcomes paclitaxel resistance and lacks neurotoxicity, which are the main obstacles limiting clinical applications of paclitaxel. Moreover, S-40 harbors the ability to inhibit growth of cancer cell lines as well as patient-derived organoids, induce mitotic arrest and cell apoptosis. Xenograft mouse models of human prostate cancer DU145, non-small cell lung cancer NCI-H1299 and paclitaxel-resistant A549 were strongly restrained without apparent side effects by S-40 oral administration once daily. These findings provide evidence for the development of S-40 as the next generation of orally effective microtubule inhibitors for cancer therapy. PubMed: 32931884DOI: 10.1016/j.canlet.2020.08.040 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.4 Å) |
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