8R6O

Tubulin-4AZA2996 complex

Summary for 8R6O

• Entry DOI: 10.2210/pdb8r6o/pdb
• Descriptor: Detyrosinated tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• Functional Keywords: cell cycle, tubulin fold, cytoskeleton, microtubule
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 6
• Total formula weight: 265223.08

Authors

Herman, J.,Vanstreels, E.,Bardiot, D.,Prota, A.E.,Olieric, N.,Gao, L.-J.,Vercruysse, T.,Daems, T.,Waer, M.,Herdewijn, P.,Louat, T.,Steinmetz, M.O.,De Jonghe, S.,Sprangers, B.,Daelemans, D. (deposition date: 2023-11-22, release date: 2024-11-27)

Primary citation

Herman, J.,Vanstreels, E.,Bardiot, D.,Prota, A.E.,Gaillard, N.,Gao, L.J.,Vercruysse, T.,Persoons, L.,Daems, T.,Waer, M.,Herdewijn, P.,Louat, T.,Steinmetz, M.O.,De Jonghe, S.,Sprangers, B.,Daelemans, D.
3-nitropyridine analogues as novel microtubule-targeting agents.
Plos One, 19:e0307153-e0307153, 2024

PubMed Abstract: Microtubule-targeting agents are an important class of anti-cancer drugs; their full potential is however not realized because of significant myelotoxicity and neurotoxicity. We here report 3-nitropyridine analogues as a novel group of microtubule-targeting agents with potent anti-cancer effects against a broad range of cancer types. We show that these 3-nitropyridines induce cell cycle arrest in the G2-M phase and inhibit tubulin polymerization by interacting with tubulin. Determination of the tubulin-4AZA2996 structure by X-ray crystallography demonstrated that this class of compounds binds to the colchicine-site of tubulin. Furthermore, the anti-cancer effect was demonstrated both in vitro and in vivo in a murine heterotopic xenograft model of colon cancer. When administered intravenously, 4AZA2891 effectively inhibited cancer growth. Whereas 3-nitropyridine compounds do not induce myelotoxicity at pharmacological doses, the neurotoxicity associated with microtubule-targeting agents is still present.

PubMed: 39509402
DOI: 10.1371/journal.pone.0307153

Experimental method

X-RAY DIFFRACTION (2.2 Å)