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Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design.
Lee KL, Ambler CM, Anderson DR, Boscoe BP, Bree AG, Brodfuehrer JI, Chang JS, Choi C, Chung S, Curran KJ, Day JE, Dehnhardt CM, Dower K, Drozda SE, Frisbie RK, Gavrin LK, Goldberg JA, Han S, Hegen M, Hepworth D, Hope HR, Kamtekar S, Kilty IC, Lee A, Lin LL, Lovering FE, Lowe MD, Mathias JP, Morgan HM, Murphy EA, Papaioannou N, Patny A, Pierce BS, Rao VR, Saiah E, Samardjiev IJ, Samas BM, Shen MWH, Shin JH, Soutter HH, Strohbach JW, Symanowicz PT, Thomason JR, Trzupek JD, Vargas R, Vincent F, Yan J, Zapf CW, Wright SW. Lee KL, et al. Among authors: rao vr. J Med Chem. 2017 Jul 13;60(13):5521-5542. doi: 10.1021/acs.jmedchem.7b00231. Epub 2017 Jun 14. J Med Chem. 2017. PMID: 28498658
Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4.
Tumey LN, Boschelli DH, Bhagirath N, Shim J, Murphy EA, Goodwin D, Bennett EM, Wang M, Lin LL, Press B, Shen M, Frisbie RK, Morgan P, Mohan S, Shin J, Rao VR. Tumey LN, et al. Among authors: rao vr. Bioorg Med Chem Lett. 2014 May 1;24(9):2066-72. doi: 10.1016/j.bmcl.2014.03.056. Epub 2014 Mar 29. Bioorg Med Chem Lett. 2014. PMID: 24726805
The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial.
Winkler A, Sun W, De S, Jiao A, Sharif MN, Symanowicz PT, Athale S, Shin JH, Wang J, Jacobson BA, Ramsey SJ, Dower K, Andreyeva T, Liu H, Hegen M, Homer BL, Brodfuehrer J, Tilley M, Gilbert SA, Danto SI, Beebe JJ, Barnes BJ, Pascual V, Lin LL, Kilty I, Fleming M, Rao VR. Winkler A, et al. Among authors: rao vr. Arthritis Rheumatol. 2021 Dec;73(12):2206-2218. doi: 10.1002/art.41953. Epub 2021 Nov 1. Arthritis Rheumatol. 2021. PMID: 34423919 Free PMC article. Clinical Trial.
Interleukin 1/Toll-like receptor-induced autophosphorylation activates interleukin 1 receptor-associated kinase 4 and controls cytokine induction in a cell type-specific manner.
Cushing L, Stochaj W, Siegel M, Czerwinski R, Dower K, Wright Q, Hirschfield M, Casanova JL, Picard C, Puel A, Lin LL, Rao VR. Cushing L, et al. Among authors: rao vr. J Biol Chem. 2014 Apr 11;289(15):10865-10875. doi: 10.1074/jbc.M113.544809. Epub 2014 Feb 24. J Biol Chem. 2014. PMID: 24567333 Free PMC article.
Characterization of (2R, 3S)-2-([[4-(2-butynyloxy)phenyl]sulfonyl]amino)-N,3-dihydroxybutanamide, a potent and selective inhibitor of TNF-alpha converting enzyme.
Zhang Y, Hegen M, Xu J, Keith JC Jr, Jin G, Du X, Cummons T, Sheppard BJ, Sun L, Zhu Y, Rao VR, Wang Q, Xu W, Cowling R, Nickerson-Nutter CL, Gibbons J, Skotnicki J, Lin LL, Levin J. Zhang Y, et al. Among authors: rao vr. Int Immunopharmacol. 2004 Dec 20;4(14):1845-57. doi: 10.1016/j.intimp.2004.08.003. Int Immunopharmacol. 2004. PMID: 15531300
355 results