Discovery and Preclinical Characterization of BIIB129, a Covalent, Selective, and Brain-Penetrant BTK Inhibitor for the Treatment of Multiple Sclerosis.

Autor: Himmelbauer MK; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Bajrami B; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Basile R; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Capacci A; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Chen T; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Choi CK; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Gilfillan R; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Gonzalez-Lopez de Turiso F; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Gu C; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Hoemberger M; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Johnson DS; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Jones JH; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Kadakia E; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Kirkland M; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Lin EY; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Liu Y; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Ma B; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Magee T; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Mantena S; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Marx IE; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Metrick CM; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Mingueneau M; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Murugan P; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Muste CA; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Nadella P; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Nevalainen M; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Parker Harp CR; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Pattaropong V; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Pietrasiewicz A; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Prince RJ; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Purgett TJ; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Santoro JC; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Schulz J; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Sciabola S; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Tang H; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Vandeveer HG; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Wang T; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Yousaf Z; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Helal CJ; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Hopkins BT; Biogen Research and Development, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2024 May 23; Vol. 67 (10), pp. 8122-8140. Date of Electronic Publication: 2024 May 07.

Discovery of Potent, Selective, and Brain-Penetrant Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitors that Modulate Brain Inflammation In Vivo .

Autor: Jones JH; Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Xin Z; Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Himmelbauer M; Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Dechantsreiter M; Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Enyedy I; Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Hedde J; Acute Neurology Research Unit, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Fang T; Acute Neurology Research Unit, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Coomaraswamy J; Movement Disorders Research Unit, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., King KW; Drug Metabolism and Pharmacokinetics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Murugan P; Bioassays, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Santoro JC; Bioassays, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Hesson T; Bioassays, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Walther DM; Chemical Biology and Proteomics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Wei R; Chemical Biology and Proteomics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Zheng F; Technical Development, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Marcotte DJ; Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Spilker K; Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Kumar PR; Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Liu Y; Drug Metabolism and Pharmacokinetics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Gilfillan R; Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Gonzalez-Lopez de Turiso F; Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2021 Oct 28; Vol. 64 (20), pp. 15402-15419. Date of Electronic Publication: 2021 Oct 15.

Discovery and in Vivo Evaluation of the Potent and Selective PI3Kδ Inhibitors 2-((1S)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-0687) and 2-((1S)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-5-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-1430).

Autor: Gonzalez-Lopez de Turiso F; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Hao X; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Shin Y; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Bui M; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Campuzano ID; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Cardozo M; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Dunn MC; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Duquette J; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Fisher B; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Foti RS; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Henne K; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., He X; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Hu YL; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Kelly RC; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Johnson MG; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Lucas BS; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., McCarter J; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., McGee LR; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Medina JC; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Metz D; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., San Miguel T; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Mohn D; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Tran T; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Vissinga C; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Wannberg S; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Whittington DA; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Whoriskey J; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Yu G; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Zalameda L; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Zhang X; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States., Cushing TD; Department of Therapeutic Discovery, §Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.; Department of Therapeutic Discovery, #Department of Inflammation Research, ⊥Drug Product Technologies, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.; Department of Therapeutic Discovery, ¶Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2016 Aug 11; Vol. 59 (15), pp. 7252-67. Date of Electronic Publication: 2016 Jul 25.

Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development.

Autor: Sun D; Departments of Therapeutic Discovery, ‡Pharmaceutics, and §Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California, 94080, United States., Li Z, Rew Y, Gribble M, Bartberger MD, Beck HP, Canon J, Chen A, Chen X, Chow D, Deignan J, Duquette J, Eksterowicz J, Fisher B, Fox BM, Fu J, Gonzalez AZ, Gonzalez-Lopez De Turiso F, Houze JB, Huang X, Jiang M, Jin L, Kayser F, Liu JJ, Lo MC, Long AM, Lucas B, McGee LR, McIntosh J, Mihalic J, Oliner JD, Osgood T, Peterson ML, Roveto P, Saiki AY, Shaffer P, Toteva M, Wang Y, Wang YC, Wortman S, Yakowec P, Yan X, Ye Q, Yu D, Yu M, Zhao X, Zhou J, Zhu J, Olson SH, Medina JC

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2014 Feb 27; Vol. 57 (4), pp. 1454-72. Date of Electronic Publication: 2014 Feb 05.

Discovery and in vivo evaluation of dual PI3Kβ/δ inhibitors.

Autor: Gonzalez-Lopez de Turiso F; Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, USA. felgonza@amgen.com, Shin Y, Brown M, Cardozo M, Chen Y, Fong D, Hao X, He X, Henne K, Hu YL, Johnson MG, Kohn T, Lohman J, McBride HJ, McGee LR, Medina JC, Metz D, Miner K, Mohn D, Pattaropong V, Seganish J, Simard JL, Wannberg S, Whittington DA, Yu G, Cushing TD

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2012 Sep 13; Vol. 55 (17), pp. 7667-85. Date of Electronic Publication: 2012 Aug 29.