6v79

Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (CD2) complexed with NF2376

spinqualitylabelsall models 6v79, resolution 2.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6v79 is a 2 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 2.0395153Å Ligands: EDO, K, QQD, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F8W4B7_DANRE Publication Abstract from PubMed Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed by our immunohistochemistry studies on HDAC6 overexpression in IPF lung tissues. We herein developed a series of novel hHDAC6 inhibitors, having low inhibitory potency over hHDAC1 and hHDAC8, as potential pharmacological tools for IPF treatment. Their inhibitory potency was combined with low in vitro and in vivo toxicity. Structural analysis of 6h and structure-activity relationship studies contributed to the optimization of the binding mode of the new molecules. The best-performing analogues were tested for their efficacy in inhibiting fibrotic sphere formation and cell viability, proving their capability in reverting the IPF phenotype. The efficacy of analogue 6h was also determined in a validated human lung model of TGF-beta1-dependent fibrogenesis. The results highlighted in this manuscript may pave the way for the identification of first-in-class molecules for the treatment of IPF. Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors.,Campiani G, Cavella C, Osko JD, Brindisi M, Relitti N, Brogi S, Saraswati AP, Federico S, Chemi G, Maramai S, Carullo G, Jaeger B, Carleo A, Benedetti R, Sarno F, Lamponi S, Rottoli P, Bargagli E, Bertucci C, Tedesco D, Herp D, Senger J, Ruberti G, Saccoccia F, Saponara S, Gorelli B, Valoti M, Kennedy B, Sundaramurthi H, Butini S, Jung M, Roach KM, Altucci L, Bradding P, Christianson DW, Gemma S, Prasse A J Med Chem. 2021 Jul 22;64(14):9960-9988. doi: 10.1021/acs.jmedchem.1c00184. Epub, 2021 Jul 12. PMID:34251197 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone deacetylase 3D structures

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