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The Discovery of 3-((4-Chloro-3-methoxyphenyl)amino)-1-((3R,4S)-4-cyanotetrahydro-2H-pyran-3-yl)-1H-pyrazole-4-carboxamide, a Highly Ligand Efficient and Efficacious Janus Kinase 1 Selective Inhibitor with Favorable Pharmacokinetic Properties.
Siu T, Brubaker J, Fuller P, Torres L, Zeng H, Close J, Mampreian DM, Shi F, Liu D, Fradera X, Johnson K, Bays N, Kadic E, He F, Goldenblatt P, Shaffer L, Patel SB, Lesburg CA, Alpert C, Dorosh L, Deshmukh SV, Yu H, Klappenbach J, Elwood F, Dinsmore CJ, Fernandez R, Moy L, Young JR. Siu T, et al. Among authors: johnson k. J Med Chem. 2017 Dec 14;60(23):9676-9690. doi: 10.1021/acs.jmedchem.7b01135. Epub 2017 Dec 4. J Med Chem. 2017. PMID: 29156136
Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials.
Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY. Marsilje TH, et al. Among authors: johnson k. J Med Chem. 2013 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26. J Med Chem. 2013. PMID: 23742252
Discovery of trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as potent, orally bioavailable TGR5 (GPBAR1) agonists: structure-activity relationships, lead optimization, and chronic in vivo efficacy.
Phillips DP, Gao W, Yang Y, Zhang G, Lerario IK, Lau TL, Jiang J, Wang X, Nguyen DG, Bhat BG, Trotter C, Sullivan H, Welzel G, Landry J, Chen Y, Joseph SB, Li C, Gordon WP, Richmond W, Johnson K, Bretz A, Bursulaya B, Pan S, McNamara P, Seidel HM. Phillips DP, et al. Among authors: johnson k. J Med Chem. 2014 Apr 24;57(8):3263-82. doi: 10.1021/jm401731q. Epub 2014 Apr 4. J Med Chem. 2014. PMID: 24666203
Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers.
Lelais G, Epple R, Marsilje TH, Long YO, McNeill M, Chen B, Lu W, Anumolu J, Badiger S, Bursulaya B, DiDonato M, Fong R, Juarez J, Li J, Manuia M, Mason DE, Gordon P, Groessl T, Johnson K, Jia Y, Kasibhatla S, Li C, Isbell J, Spraggon G, Bender S, Michellys PY. Lelais G, et al. Among authors: johnson k. J Med Chem. 2016 Jul 28;59(14):6671-89. doi: 10.1021/acs.jmedchem.5b01985. Epub 2016 Jul 19. J Med Chem. 2016. PMID: 27433829
Tetrahydrofuran-Based Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonists: Ligand-Based Discovery, Activity in a Rodent Asthma Model, and Mechanism-of-Action via Cryogenic Electron Microscopy.
Terrett JA, Chen H, Shore DG, Villemure E, Larouche-Gauthier R, Déry M, Beaumier F, Constantineau-Forget L, Grand-Maître C, Lépissier L, Ciblat S, Sturino C, Chen Y, Hu B, Lu A, Wang Y, Cridland AP, Ward SI, Hackos DH, Reese RM, Shields SD, Chen J, Balestrini A, Riol-Blanco L, Lee WP, Liu J, Suto E, Wu X, Zhang J, Ly JQ, La H, Johnson K, Baumgardner M, Chou KJ, Rohou A, Rougé L, Safina BS, Magnuson S, Volgraf M. Terrett JA, et al. Among authors: johnson k. J Med Chem. 2021 Apr 8;64(7):3843-3869. doi: 10.1021/acs.jmedchem.0c02023. Epub 2021 Mar 22. J Med Chem. 2021. PMID: 33749283
Discovery of TRPA1 Antagonist GDC-6599: Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease.
Terrett JA, Ly JQ, Katavolos P, Hasselgren C, Laing S, Zhong F, Villemure E, Déry M, Larouche-Gauthier R, Chen H, Shore DG, Lee WP, Suto E, Johnson K, Brooks M, Stablein A, Beaumier F, Constantineau-Forget L, Grand-Maître C, Lépissier L, Ciblat S, Sturino C, Chen Y, Hu B, Elstrott J, Gandham V, Joseph V, Booler H, Cain G, Chou C, Fullerton A, Lepherd M, Stainton S, Torres E, Urban K, Yu L, Zhong Y, Bao L, Chou KJ, Lin J, Zhang W, La H, Liu L, Mulder T, Chen J, Chernov-Rogan T, Johnson AR, Hackos DH, Leahey R, Shields SD, Balestrini A, Riol-Blanco L, Safina BS, Volgraf M, Magnuson S, Kakiuchi-Kiyota S. Terrett JA, et al. Among authors: johnson ar, johnson k. J Med Chem. 2024 Mar 14;67(5):3287-3306. doi: 10.1021/acs.jmedchem.3c02121. Epub 2024 Mar 3. J Med Chem. 2024. PMID: 38431835
Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases.
Nagle A, Biggart A, Be C, Srinivas H, Hein A, Caridha D, Sciotti RJ, Pybus B, Kreishman-Deitrick M, Bursulaya B, Lai YH, Gao MY, Liang F, Mathison CJN, Liu X, Yeh V, Smith J, Lerario I, Xie Y, Chianelli D, Gibney M, Berman A, Chen YL, Jiricek J, Davis LC, Liu X, Ballard J, Khare S, Eggimann FK, Luneau A, Groessl T, Shapiro M, Richmond W, Johnson K, Rudewicz PJ, Rao SPS, Thompson C, Tuntland T, Spraggon G, Glynne RJ, Supek F, Wiesmann C, Molteni V. Nagle A, et al. Among authors: johnson k. J Med Chem. 2020 Oct 8;63(19):10773-10781. doi: 10.1021/acs.jmedchem.0c00499. Epub 2020 Jul 29. J Med Chem. 2020. PMID: 32667203 Free PMC article.
Biotransformation novel advances - 2021 year in review.
Khojasteh SC, Argikar UA, Cho S, Crouch R, Heck CJS, Johnson KM, Kalgutkar AS, King L, Maw HH, Seneviratne HK, Wang S, Wei C, Zhang D, Jackson KD. Khojasteh SC, et al. Drug Metab Rev. 2022 Aug;54(3):207-245. doi: 10.1080/03602532.2022.2097253. Epub 2022 Aug 30. Drug Metab Rev. 2022. PMID: 35815654 Free PMC article. Review.
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