94294-09-4Relevant academic research and scientific papers
Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors
Alen, Jo,Schade, Markus,Wagener, Markus,Christian, Frank,Nordhoff, Sonja,Merla, Beatrix,Dunkern, Torsten R.,Bahrenberg, Gregor,Ratcliffe, Paul
supporting information, p. 6391 - 6397 (2019/07/08)
Genome-wide-association studies in chronic low back pain patients identified sepiapterin reductase as a high interest target for developing new analgesics. Here we used 19F NMR fragment screening for the discovery of novel, ligand-efficient SPR
METHODS AND COMPOSITIONS FOR INHIBITING RHO/MRTF-MEDIATED DISEASES AND CONDITIONS
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, (2015/09/28)
The present disclosure relates to methods, compositions, and kits for the inhibition of signaling by members of the Rho GTPase family. Specifically, the disclosure relates to methods, compositions and kits for the inhibition of RhoA and/or RhoC transcriptional signaling and action of the transcription co-factors MRTF-A and/or MRTF-B. The disclosure finds use in treatment of Rho-mediated disease states (e.g., tumor metastasis and fibrosis), Rho-mediated biological conditions, and in cell signaling research.
METHODS AND COMPOSITIONS FOR INHIBITING RHO/MRTF-MEDIATED DISEASES AND CONDITIONS
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Page/Page column 59, (2015/10/05)
The present disclosure relates to methods, compositions, and kits for the inhibition of signaling by members of the Rho GTPase family. Specifically, the disclosure relates to methods, compositions and kits for the inhibition of RhoA and/or RhoC transcriptional signaling and action os the transcripton co-factors MRTF-A and/or MRTF-B. The disclosure finds use in treatment of Rho-mediated disease states (e.g., tumor metastasis and fibrosis), Rho-mediated biological conditions, and in cell signaling research.
Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitors
Liang, Jun,Van Abbema, Anne,Balazs, Mercedesz,Barrett, Kathy,Berezhkovsky, Leo,Blair, Wade,Chang, Christine,Delarosa, Donnie,Devoss, Jason,Driscoll, Jim,Eigenbrot, Charles,Ghilardi, Nico,Gibbons, Paul,Halladay, Jason,Johnson, Adam,Kohli, Pawan Bir,Lai, Yingjie,Liu, Yanzhou,Lyssikatos, Joseph,Mantik, Priscilla,Menghrajani, Kapil,Murray, Jeremy,Peng, Ivan,Sambrone, Amy,Shia, Steven,Shin, Young,Smith, Jan,Sohn, Sue,Tsui, Vickie,Ultsch, Mark,Wu, Lawren C.,Xiao, Yisong,Yang, Wenqian,Young, Judy,Zhang, Birong,Zhu, Bing-Yan,Magnuson, Steven
supporting information, p. 4521 - 4536 (2013/07/25)
Herein we report our lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead molecule 3. We used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1 and JAK2 selectivity relative to 3. Further optimization eventually led to compound 37 that showed good TYK2 enzyme and interleukin-12 (IL-12) cell potency, as well as acceptable cellular JAK1 and JAK2 selectivity and excellent oral exposure in mice. When tested in a mouse IL-12 PK/PD model, compound 37 showed statistically significant knockdown of cytokine interferon-γ (IFNγ), suggesting that selective inhibition of TYK2 kinase activity might be sufficient to block the IL-12 pathway in vivo.
3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Inhibitors. 3. 7-(3,5-Disubstituted -2-yl)-3,5-dihydroxy-6-heptenoic Acids and Their Lactone Derivatives
Stokker, G. E.,Alberts, A. W.,Anderson, P. S.,Cragoe, E. J.,Deana, A. A.,et al.
, p. 170 - 181 (2007/10/02)
The syntheses of a series of 7-(3,5-disubstituted -2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactones are reported.Intrinsic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity is enhanced markedly when the biphenyl mo
