6V7A

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

Summary for 6V7A

• Entry DOI: 10.2210/pdb6v7a/pdb
• Descriptor: Hdac6 protein, ZINC ION, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: histone deacetylase, hydrolase
• Biological source: Danio rerio (Zebrafish)
• Total number of polymer chains: 1
• Total formula weight: 40780.53

Authors

Osko, J.D.,Christianson, D.W. (deposition date: 2019-12-08, release date: 2020-12-02, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.08741757573 Å)