6V7A

Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (CD2) complexed with NF2657

6V7A の概要

• エントリーDOI: 10.2210/pdb6v7a/pdb
• 分子名称: Hdac6 protein, ZINC ION, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: histone deacetylase, hydrolase
• 由来する生物種: Danio rerio (Zebrafish)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40780.53

構造登録者

Osko, J.D.,Christianson, D.W. (登録日: 2019-12-08, 公開日: 2020-12-02, 最終更新日: 2023-10-11)

主引用文献

Saraswati, A.P.,Relitti, N.,Brindisi, M.,Osko, J.D.,Chemi, G.,Federico, S.,Grillo, A.,Brogi, S.,McCabe, N.H.,Turkington, R.C.,Ibrahim, O.,O'Sullivan, J.,Lamponi, S.,Ghanim, M.,Kelly, V.P.,Zisterer, D.,Amet, R.,Hannon Barroeta, P.,Vanni, F.,Ulivieri, C.,Herp, D.,Sarno, F.,Di Costanzo, A.,Saccoccia, F.,Ruberti, G.,Jung, M.,Altucci, L.,Gemma, S.,Butini, S.,Christianson, D.W.,Campiani, G.
Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation.
Acs Med.Chem.Lett., 11:2268-2276, 2020

PubMed Abstract: Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report the development of a series of spiroindoline-based HDAC6 isoform-selective inhibitors based on the X-ray crystal studies of the hit . We identified compound as the most potent and selective HDAC6 inhibitor of the series. Biological investigation of compounds , , and demonstrated their antiproliferative activity against several cancer cell lines. Western blotting studies indicated that they were able to increase tubulin acetylation, without significant variation in histone acetylation state, and induced PARP cleavage indicating their apoptotic potential at the molecular level. induced HDAC6-dependent pSTAT3 inhibition.

PubMed: 33214839
DOI: 10.1021/acsmedchemlett.0c00395

実験手法

X-RAY DIFFRACTION (2.08741757573 Å)