6TDE

Tubulin-inhibitor complex

6TDE の概要

• エントリーDOI: 10.2210/pdb6tde/pdb
• 分子名称: Tubulin alpha chain, Tubulin beta chain, Stathmin-4, ... (9 entities in total)
• 機能のキーワード: cytoskeleton, cell division, intracellular transport, cell cycle
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 220791.47

構造登録者

Varela, P.F.,Gigant, B. (登録日: 2019-11-08, 公開日: 2020-09-02, 最終更新日: 2024-11-20)

主引用文献

Shchegravina, E.S.,Svirshchevskaya, E.V.,Combes, S.,Allegro, D.,Barbier, P.,Gigant, B.,Varela, P.F.,Gavryushin, A.E.,Kobanova, D.A.,Shchekotikhin, A.E.,Fedorov, A.Y.
Discovery of dihydrofuranoallocolchicinoids - Highly potent antimitotic agents with low acute toxicity.
Eur.J.Med.Chem., 207:112724-112724, 2020

PubMed Abstract: Two series of heterocyclic colchicinoids bearing β-methylenedihydrofuran or 2H-pyran-2-one fragments were synthesized by the intramolecular Heck reaction. Methylenedihydrofuran compounds 9a and 9h were found to be the most cytotoxic among currently known colchicinoids, exhibiting outstanding antiproliferative activity on tumor cell lines in picomolar (0.01-2.1 nM) range of concentrations. Compound 9a potently and substoichiometrically inhibits microtubule formation in vitro, being an order of magnitude more active in this assay than colchicine. Derivatives 9a and 9h revealed relatively low acute toxicity in mice (LD ≥ 10 mg/kg i.v.). The X-Ray structure of colchicinoid 9a bound to tubulin confirmed interaction of this compound with the colchicine binding site of tubulin.

PubMed: 32827941
DOI: 10.1016/j.ejmech.2020.112724

実験手法

X-RAY DIFFRACTION (2.286 Å)