6tde
From Proteopedia
Tubulin-inhibitor complex
Structural highlights
FunctionD0VWZ0_SHEEP Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).[RuleBase:RU003505][SAAS:SAAS023123_004_019801] Publication Abstract from PubMedTwo series of heterocyclic colchicinoids bearing beta-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(50) >/= 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. Discovery of dihydrofuranoallocolchicinoids - Highly potent antimitotic agents with low acute toxicity.,Shchegravina ES, Svirshchevskaya EV, Combes S, Allegro D, Barbier P, Gigant B, Varela PF, Gavryushin AE, Kobanova DA, Shchekotikhin AE, Fedorov AY Eur J Med Chem. 2020 Dec 1;207:112724. doi: 10.1016/j.ejmech.2020.112724. Epub , 2020 Aug 13. PMID:32827941[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
