Discovery of a structural class of antibiotics with explainable deep learning.

Autor: Wong F; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Integrated Biosciences, San Carlos, CA, USA., Zheng EJ; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Program in Chemical Biology, Harvard University, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Valeri JA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Donghia NM; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Anahtar MN; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Omori S; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Integrated Biosciences, San Carlos, CA, USA., Li A; Integrated Biosciences, San Carlos, CA, USA., Cubillos-Ruiz A; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Krishnan A; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Jin W; Eric and Wendy Schmidt Center, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Manson AL; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Friedrichs J; Leibniz Institute of Polymer Research and the Max Bergmann Center of Biomaterials, Dresden, Germany., Helbig R; Leibniz Institute of Polymer Research and the Max Bergmann Center of Biomaterials, Dresden, Germany., Hajian B; Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Fiejtek DK; Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Wagner FF; Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Soutter HH; Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Earl AM; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Stokes JM; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research and David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, Canada., Renner LD; Leibniz Institute of Polymer Research and the Max Bergmann Center of Biomaterials, Dresden, Germany., Collins JJ; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. jimjc@mit.edu.; Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. jimjc@mit.edu.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. jimjc@mit.edu.

Publikováno v: Nature [Nature] 2024 Feb; Vol. 626 (7997), pp. 177-185. Date of Electronic Publication: 2023 Dec 20.

Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action.

Autor: Fernández-Montalván AE; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Berger M; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Kuropka B; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Koo SJ; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Badock V; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Weiske J; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Puetter V; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Holton SJ; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Stöckigt D; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Ter Laak A; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Centrella PA; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Clark MA; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Dumelin CE; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Sigel EA; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Soutter HH; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Troast DM; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Zhang Y; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Cuozzo JW; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Keefe AD; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Roche D; Edelris , Lyon, France., Rodeschini V; Edelris , Lyon, France., Chaikuad A; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Díaz-Sáez L; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Bennett JM; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Fedorov O; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Huber KVM; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Hübner J; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Weinmann H; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Hartung IV; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Gorjánácz M; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany.

Publikováno v: ACS chemical biology [ACS Chem Biol] 2017 Nov 17; Vol. 12 (11), pp. 2730-2736. Date of Electronic Publication: 2017 Oct 24.

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.

Autor: 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; Worldwide Medicinal Chemistry, Pfizer Inc. , 1070 Science Center Drive, San Diego, California 92121, United States., 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; Worldwide Medicinal Chemistry, Pfizer Inc. , 1070 Science Center Drive, San Diego, California 92121, United States., Zapf CW, Wright SW

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2017 Jul 13; Vol. 60 (13), pp. 5521-5542. Date of Electronic Publication: 2017 Jun 14.

Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors.

Autor: Johannes JW; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Bates S; AstraZeneca R&D Cambridge Science Park , Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Beigie C; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Belmonte MA; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Breen J; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Cao S; Pharmaron Beijing Co., Ltd. 6 Taihe Road BDA, Beijing 100176 P. R. China., Centrella PA; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Clark MA; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Cuozzo JW; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Dumelin CE; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Ferguson AD; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Habeshian S; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Hargreaves D; AstraZeneca R&D Cambridge Science Park , Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Joubran C; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Kazmirski S; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Keefe AD; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Lamb ML; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Lan H; Pharmaron Beijing Co., Ltd. 6 Taihe Road BDA, Beijing 100176 P. R. China., Li Y; Pharmaron Beijing Co., Ltd. 6 Taihe Road BDA, Beijing 100176 P. R. China., Ma H; Pharmaron Beijing Co., Ltd. 6 Taihe Road BDA, Beijing 100176 P. R. China., Mlynarski S; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Packer MJ; AstraZeneca R&D Alderley Park , Macclesfield, Cheshire SK10 4TG, United Kingdom., Rawlins PB; AstraZeneca R&D Cambridge Science Park , Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Robbins DW; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Shen H; Pharmaron Beijing Co., Ltd. 6 Taihe Road BDA, Beijing 100176 P. R. China., Sigel EA; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Soutter HH; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Su N; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Troast DM; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Wang H; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Wickson KF; AstraZeneca R&D Cambridge Science Park , Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Wu C; Pharmaron Beijing Co., Ltd. 6 Taihe Road BDA, Beijing 100176 P. R. China., Zhang Y; X-Chem Pharmaceuticals , 100 Beaver Street, Waltham, Massachusetts 02453, United States., Zhao Q; Pharmaron Beijing Co., Ltd. 6 Taihe Road BDA, Beijing 100176 P. R. China., Zheng X; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Hird AW; AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.

Publikováno v: ACS medicinal chemistry letters [ACS Med Chem Lett] 2016 Dec 27; Vol. 8 (2), pp. 239-244. Date of Electronic Publication: 2016 Dec 27 (Print Publication: 2017).

Overview of Recent Progress in Protein-Expression Technologies for Small-Molecule Screening.

Autor: Cuozzo JW; X-Chem, Inc., Waltham, MA, USA jcuozzo@x-chemrx.com., Soutter HH; X-Chem, Inc., Waltham, MA, USA.

Publikováno v: Journal of biomolecular screening [J Biomol Screen] 2014 Aug; Vol. 19 (7), pp. 1000-13. Date of Electronic Publication: 2014 Feb 13.