92040-00-1Relevant articles and documents
Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors
Campiani, Giuseppe,Cavella, Caterina,Osko, Jeremy D.,Brindisi, Margherita,Relitti, Nicola,Brogi, Simone,Saraswati, A. Prasanth,Federico, Stefano,Chemi, Giulia,Maramai, Samuele,Carullo, Gabriele,Jaeger, Benedikt,Carleo, Alfonso,Benedetti, Rosaria,Sarno, Federica,Lamponi, Stefania,Rottoli, Paola,Bargagli, Elena,Bertucci, Carlo,Tedesco, Daniele,Herp, Daniel,Senger, Johanna,Ruberti, Giovina,Saccoccia, Fulvio,Saponara, Simona,Gorelli, Beatrice,Valoti, Massimo,Kennedy, Breándan,Sundaramurthi, Husvinee,Butini, Stefania,Jung, Manfred,Roach, Katy M.,Altucci, Lucia,Bradding, Peter,Christianson, David W.,Gemma, Sandra,Prasse, Antje
, p. 9960 - 9988 (2021/07/31)
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 novelhHDAC6 inhibitors, having low inhibitory potency overhHDAC1 andhHDAC8, as potential pharmacological tools for IPF treatment. Their inhibitory potency was combined with lowin vitroandin vivotoxicity. 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-β1-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.
INDAZOLE COMPOUNDS AS KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
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Page/Page column 126, (2013/04/25)
The present teaching provide indazole compounds represented by Structural Formulae (I) or (I') or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof as protein kinase inhibitors, such as T
Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors
Pajouhesh, Hassan,Feng, Zhong-Ping,Ding, Yanbing,Zhang, Lingyun,Pajouhesh, Hossein,Morrison, Jerrie-Lynn,Belardetti, Francesco,Tringham, Elizabeth,Simonson, Eric,Vanderah, Todd W.,Porreca, Frank,Zamponi, Gerald W.,Mitscher, Lester A.,Snutch, Terrance P.
scheme or table, p. 1378 - 1383 (2010/07/06)
A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC50 values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.
