6v7a

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

spinqualitylabelsall models 6v7a, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6v7a is a 1 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.0874176Å Ligands: K, QQG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F8W4B7_DANRE Publication Abstract from PubMed 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 6a. We identified compound 6j as the most potent and selective hHDAC6 inhibitor of the series. Biological investigation of compounds 6b, 6h, and 6j 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. 6j induced HDAC6-dependent pSTAT3 inhibition. Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation.,Saraswati AP, Relitti N, Brindisi M, Osko JD, Chemi G, Federico S, Grillo A, Brogi S, McCabe NH, Turkington RC, Ibrahim O, O'Sullivan J, Lamponi S, Ghanim M, Kelly VP, 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 DW, Campiani G ACS Med Chem Lett. 2020 Sep 29;11(11):2268-2276. doi: , 10.1021/acsmedchemlett.0c00395. eCollection 2020 Nov 12. PMID:33214839 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone deacetylase 3D structures

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