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Page 1
Discovery and Optimization of Potent, Selective, and Brain-Penetrant 1-Heteroaryl-1H-Indazole LRRK2 Kinase Inhibitors for the Treatment of Parkinson's Disease.
Candito DA, Simov V, Gulati A, Kattar S, Chau RW, Lapointe BT, Methot JL, DeMong DE, Graham TH, Kurukulasuriya R, Keylor MH, Tong L, Morriello GJ, Acton JJ, Pio B, Liu W, Scott JD, Ardolino MJ, Martinot TA, Maddess ML, Yan X, Gunaydin H, Palte RL, McMinn SE, Nogle L, Yu H, Minnihan EC, Lesburg CA, Liu P, Su J, Hegde LG, Moy LY, Woodhouse JD, Faltus R, Xiong T, Ciaccio P, Piesvaux JA, Otte KM, Kennedy ME, Bennett DJ, DiMauro EF, Fell MJ, Neelamkavil S, Wood HB, Fuller PH, Ellis JM. Candito DA, et al. Among authors: kennedy me. J Med Chem. 2022 Dec 22;65(24):16801-16817. doi: 10.1021/acs.jmedchem.2c01605. Epub 2022 Dec 7. J Med Chem. 2022. PMID: 36475697
Discovery of a 3-(4-Pyrimidinyl) Indazole (MLi-2), an Orally Available and Selective Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitor that Reduces Brain Kinase Activity.
Scott JD, DeMong DE, Greshock TJ, Basu K, Dai X, Harris J, Hruza A, Li SW, Lin SI, Liu H, Macala MK, Hu Z, Mei H, Zhang H, Walsh P, Poirier M, Shi ZC, Xiao L, Agnihotri G, Baptista MA, Columbus J, Fell MJ, Hyde LA, Kuvelkar R, Lin Y, Mirescu C, Morrow JA, Yin Z, Zhang X, Zhou X, Chang RK, Embrey MW, Sanders JM, Tiscia HE, Drolet RE, Kern JT, Sur SM, Renger JJ, Bilodeau MT, Kennedy ME, Parker EM, Stamford AW, Nargund R, McCauley JA, Miller MW. Scott JD, et al. Among authors: kennedy me. J Med Chem. 2017 Apr 13;60(7):2983-2992. doi: 10.1021/acs.jmedchem.7b00045. Epub 2017 Mar 16. J Med Chem. 2017. PMID: 28245354
Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors.
Keylor MH, Gulati A, Kattar SD, Johnson RE, Chau RW, Margrey KA, Ardolino MJ, Zarate C, Poremba KE, Simov V, Morriello GJ, Acton JJ, Pio B, Yan X, Palte RL, McMinn SE, Nogle L, Lesburg CA, Adpressa D, Lin S, Neelamkavil S, Liu P, Su J, Hegde LG, Woodhouse JD, Faltus R, Xiong T, Ciaccio PJ, Piesvaux J, Otte KM, Wood HB, Kennedy ME, Bennett DJ, DiMauro EF, Fell MJ, Fuller PH. Keylor MH, et al. Among authors: kennedy me. J Med Chem. 2022 Jan 13;65(1):838-856. doi: 10.1021/acs.jmedchem.1c01968. Epub 2021 Dec 30. J Med Chem. 2022. PMID: 34967623
MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition.
Fell MJ, Mirescu C, Basu K, Cheewatrakoolpong B, DeMong DE, Ellis JM, Hyde LA, Lin Y, Markgraf CG, Mei H, Miller M, Poulet FM, Scott JD, Smith MD, Yin Z, Zhou X, Parker EM, Kennedy ME, Morrow JA. Fell MJ, et al. Among authors: kennedy me. J Pharmacol Exp Ther. 2015 Dec;355(3):397-409. doi: 10.1124/jpet.115.227587. Epub 2015 Sep 25. J Pharmacol Exp Ther. 2015. PMID: 26407721
Characterization of the Onset, Progression, and Reversibility of Morphological Changes in Mouse Lung after Pharmacological Inhibition of Leucine-Rich Kinase 2 Kinase Activity.
Bryce DK, Ware CM, Woodhouse JD, Ciaccio PJ, Ellis JM, Hegde LG, Kuruvilla S, Maddess ML, Markgraf CG, Otte KM, Poulet FM, Timmins LM, Kennedy ME, Fell MJ. Bryce DK, et al. Among authors: kennedy me. J Pharmacol Exp Ther. 2021 Apr;377(1):11-19. doi: 10.1124/jpet.120.000217. Epub 2021 Jan 28. J Pharmacol Exp Ther. 2021. PMID: 33509901
LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits.
Baptista MAS, Merchant K, Barrett T, Bhargava S, Bryce DK, Ellis JM, Estrada AA, Fell MJ, Fiske BK, Fuji RN, Galatsis P, Henry AG, Hill S, Hirst W, Houle C, Kennedy ME, Liu X, Maddess ML, Markgraf C, Mei H, Meier WA, Needle E, Ploch S, Royer C, Rudolph K, Sharma AK, Stepan A, Steyn S, Trost C, Yin Z, Yu H, Wang X, Sherer TB. Baptista MAS, et al. Among authors: kennedy me. Sci Transl Med. 2020 Apr 22;12(540):eaav0820. doi: 10.1126/scitranslmed.aav0820. Sci Transl Med. 2020. PMID: 32321864
Discovery of an Orally Available, Brain Penetrant BACE1 Inhibitor that Affords Robust CNS Aβ Reduction.
Stamford AW, Scott JD, Li SW, Babu S, Tadesse D, Hunter R, Wu Y, Misiaszek J, Cumming JN, Gilbert EJ, Huang C, McKittrick BA, Hong L, Guo T, Zhu Z, Strickland C, Orth P, Voigt JH, Kennedy ME, Chen X, Kuvelkar R, Hodgson R, Hyde LA, Cox K, Favreau L, Parker EM, Greenlee WJ. Stamford AW, et al. Among authors: kennedy me. ACS Med Chem Lett. 2012 Nov 8;3(11):897-902. doi: 10.1021/ml3001165. Epub 2012 Jul 12. ACS Med Chem Lett. 2012. PMID: 23412139 Free PMC article.
Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease.
Scott JD, Li SW, Brunskill AP, Chen X, Cox K, Cumming JN, Forman M, Gilbert EJ, Hodgson RA, Hyde LA, Jiang Q, Iserloh U, Kazakevich I, Kuvelkar R, Mei H, Meredith J, Misiaszek J, Orth P, Rossiter LM, Slater M, Stone J, Strickland CO, Voigt JH, Wang G, Wang H, Wu Y, Greenlee WJ, Parker EM, Kennedy ME, Stamford AW. Scott JD, et al. Among authors: kennedy me. J Med Chem. 2016 Dec 8;59(23):10435-10450. doi: 10.1021/acs.jmedchem.6b00307. Epub 2016 Nov 18. J Med Chem. 2016. PMID: 27933948
Discovery of cyclic acylguanidines as highly potent and selective beta-site amyloid cleaving enzyme (BACE) inhibitors: Part I--inhibitor design and validation.
Zhu Z, Sun ZY, Ye Y, Voigt J, Strickland C, Smith EM, Cumming J, Wang L, Wong J, Wang YS, Wyss DF, Chen X, Kuvelkar R, Kennedy ME, Favreau L, Parker E, McKittrick BA, Stamford A, Czarniecki M, Greenlee W, Hunter JC. Zhu Z, et al. Among authors: kennedy me. J Med Chem. 2010 Feb 11;53(3):951-65. doi: 10.1021/jm901408p. J Med Chem. 2010. PMID: 20043696
Discovery of potent iminoheterocycle BACE1 inhibitors.
Caldwell JP, Mazzola RD, Durkin J, Chen J, Chen X, Favreau L, Kennedy M, Kuvelkar R, Lee J, McHugh N, McKittrick B, Orth P, Stamford A, Strickland C, Voigt J, Wang L, Zhang L, Zhang Q, Zhu Z. Caldwell JP, et al. Bioorg Med Chem Lett. 2014 Dec 1;24(23):5455-9. doi: 10.1016/j.bmcl.2014.10.006. Epub 2014 Oct 23. Bioorg Med Chem Lett. 2014. PMID: 25455483
74 results