Search Results - "Hyde, Lynn"

MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition by Fell, Matthew J, Mirescu, Christian, Basu, Kallol, Cheewatrakoolpong, Boonlert, DeMong, Duane E, Ellis, J Michael, Hyde, Lynn A, Lin, Yinghui, Markgraf, Carrie G, Mei, Hong, Miller, Michael, Poulet, Frederique M, Scott, Jack D, Smith, Michelle D, Yin, Zhizhang, Zhou, Xiaoping, Parker, Eric M, Kennedy, Matthew E, Morrow, John A

“…Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of familial and sporadic Parkinson's disease (PD). That the most…”
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The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients by Kennedy, Matthew E, Stamford, Andrew W, Chen, Xia, Cox, Kathleen, Cumming, Jared N, Dockendorf, Marissa F, Egan, Michael, Ereshefsky, Larry, Hodgson, Robert A, Hyde, Lynn A, Jhee, Stanford, Kleijn, Huub J, Kuvelkar, Reshma, Li, Wei, Mattson, Britta A, Mei, Hong, Palcza, John, Scott, Jack D, Tanen, Michael, Troyer, Matthew D, Tseng, Jack L, Stone, Julie A, Parker, Eric M, Forman, Mark S

“…β-Amyloid (Aβ) peptides are thought to be critically involved in the etiology of Alzheimer's disease (AD). The aspartyl protease β-site amyloid precursor…”
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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 by Scott, Jack D, Li, Sarah W, Brunskill, Andrew P. J, Chen, Xia, Cox, Kathleen, Cumming, Jared N, Forman, Mark, Gilbert, Eric J, Hodgson, Robert A, Hyde, Lynn A, Jiang, Qin, Iserloh, Ulrich, Kazakevich, Irina, Kuvelkar, Reshma, Mei, Hong, Meredith, John, Misiaszek, Jeffrey, Orth, Peter, Rossiter, Lana M, Slater, Meagan, Stone, Julie, Strickland, Corey O, Voigt, Johannes H, Wang, Ganfeng, Wang, Hongwu, Wu, Yusheng, Greenlee, William J, Parker, Eric M, Kennedy, Matthew E, Stamford, Andrew W

“…Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein…”
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fMRI study of olfactory processing in mice under three anesthesia protocols: Insight into the effect of ketamine on olfactory processing by Zhao, Fuqiang, Meng, Xiangjun, Lu, Sherry, Hyde, Lynn A., Kennedy, Matthew E., Houghton, Andrea K., Evelhoch, Jeffrey L., Hines, Catherine D.G.

“…Functional magnetic resonance imaging (fMRI) is a valuable tool for studying neural activations in the central nervous system of animals due to its wide…”
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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 by Scott, Jack D, DeMong, Duane E, Greshock, Thomas J, Basu, Kallol, Dai, Xing, Harris, Joel, Hruza, Alan, Li, Sarah W, Lin, Sue-Ing, Liu, Hong, Macala, Megan K, Hu, Zhiyong, Mei, Hong, Zhang, Honglu, Walsh, Paul, Poirier, Marc, Shi, Zhi-Cai, Xiao, Li, Agnihotri, Gautam, Baptista, Marco A. S, Columbus, John, Fell, Matthew J, Hyde, Lynn A, Kuvelkar, Reshma, Lin, Yinghui, Mirescu, Christian, Morrow, John A, Yin, Zhizhang, Zhang, Xiaoping, Zhou, Xiaoping, Chang, Ronald K, Embrey, Mark W, Sanders, John M, Tiscia, Heather E, Drolet, Robert E, Kern, Jonathan T, Sur, Sylvie M, Renger, John J, Bilodeau, Mark T, Kennedy, Matthew E, Parker, Eric M, Stamford, Andrew W, Nargund, Ravi, McCauley, John A, Miller, Michael W

“…Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein which contains a kinase domain and GTPase domain among other regions. Individuals…”
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Pharmacological BACE Inhibition Improves Axonal Regeneration in Nerve Injury and Disease Models by Tallon, Carolyn, Marshall, Katherine L., Kennedy, Matthew E., Hyde, Lynn A., Farah, Mohamed. H.

“…While the peripheral nervous system is able to repair itself following injury and disease, recovery is often slow and incomplete, with no available treatments…”
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Design and discovery of C2-fluoroalkyl iminothiazine dioxides as BACE inhibitors by Taoka, Brandon M., Wu, Wen-Lian, Hao, Jinsong, Dolmaski, Martin, Wang, Hongwu, Levorse, Dorothy, Orth, Peter, Hyde, Lynn A., Smith, Brad, Michener, Maria S., Kennedy, Matthew E., Parker, Eric M., Cumming, Jared N.

“…[Display omitted] This paper describes the structure–activity-relationships of novel fluoroalkyl substituents at the C2 position of iminothiazine dioxide beta…”
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Inhibition of O-GlcNAcase leads to elevation of O-GlcNAc tau and reduction of tauopathy and cerebrospinal fluid tau in rTg4510 mice by Hastings, Nicholas B, Wang, Xiaohai, Song, Lixin, Butts, Brent D, Grotz, Diane, Hargreaves, Richard, Fred Hess, J, Hong, Kwok-Lam Karen, Huang, Cathy Ruey-Ruey, Hyde, Lynn, Laverty, Maureen, Lee, Julie, Levitan, Diane, Lu, Sherry X, Maguire, Maureen, Mahadomrongkul, Veeravan, McEachern, Ernest J, Ouyang, Xuesong, Rosahl, Thomas W, Selnick, Harold, Stanton, Michaela, Terracina, Giuseppe, Vocadlo, David J, Wang, Ganfeng, Duffy, Joseph L, Parker, Eric M, Zhang, Lili

“…Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative…”
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Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-AβPPswe Mice Without Inducing Microhemorrhage by Villarreal, Stephanie, Zhao, Fuqiang, Hyde, Lynn A, Holder, Daniel, Forest, Thomas, Sondey, Marie, Chen, Xia, Sur, Cyrille, Parker, Eric M, Kennedy, Matthew E

“…Verubecestat is a potent BACE1 enzyme inhibitor currently being investigated in Phase III trials for the treatment of mild-to-moderate and prodromal…”
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Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor by Cumming, Jared N., Smith, Elizabeth M., Wang, Lingyan, Misiaszek, Jeffrey, Durkin, James, Pan, Jianping, Iserloh, Ulrich, Wu, Yusheng, Zhu, Zhaoning, Strickland, Corey, Voigt, Johannes, Chen, Xia, Kennedy, Matthew E., Kuvelkar, Reshma, Hyde, Lynn A., Cox, Kathleen, Favreau, Leonard, Czarniecki, Michael F., Greenlee, William J., McKittrick, Brian A., Parker, Eric M., Stamford, Andrew W.

“…From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers…”
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MitoPark mice, an animal model of Parkinson's disease, show enhanced prepulse inhibition of acoustic startle and no loss of gating in response to the adenosine A(2A) antagonist SCH 412348 by Grauer, Steven M, Hodgson, Robert, Hyde, Lynn A

“…Psychoses are debilitating side effects associated with current dopaminergic treatments for Parkinson's disease (PD). Prepulse inhibition (PPI), in which a…”
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Structure-Based Design of an Iminoheterocyclic β‑Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central Aβ in Nonhuman Primates by Mandal, Mihirbaran, Wu, Yusheng, Misiaszek, Jeffrey, Li, Guoqing, Buevich, Alexei, Caldwell, John P, Liu, Xiaoxiang, Mazzola, Robert D, Orth, Peter, Strickland, Corey, Voigt, Johannes, Wang, Hongwu, Zhu, Zhaoning, Chen, Xia, Grzelak, Michael, Hyde, Lynn A, Kuvelkar, Reshma, Leach, Prescott T, Terracina, Giuseppe, Zhang, Lili, Zhang, Qi, Michener, Maria S, Smith, Brad, Cox, Kathleen, Grotz, Diane, Favreau, Leonard, Mitra, Kaushik, Kazakevich, Irina, McKittrick, Brian A, Greenlee, William, Kennedy, Matthew E, Parker, Eric M, Cumming, Jared N, Stamford, Andrew W

“…We describe successful efforts to optimize the in vivo profile and address off-target liabilities of a series of BACE1 inhibitors represented by 6 that…”
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Analysis of tau post-translational modifications in rTg4510 mice, a model of tau pathology by Song, Lixin, Lu, Sherry X, Ouyang, Xuesong, Melchor, Jerry, Lee, Julie, Terracina, Giuseppe, Wang, Xiaohai, Hyde, Lynn, Hess, J Fred, Parker, Eric M, Zhang, Lili

“…Microtubule associated protein tau is the major component of the neurofibrillary tangles (NFTs) found in the brains of patients with Alzheimer's disease and…”
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Design and Validation of Bicyclic Iminopyrimidinones As Beta Amyloid Cleaving Enzyme‑1 (BACE1) Inhibitors: Conformational Constraint to Favor a Bioactive Conformation by Mandal, Mihirbaran, Zhu, Zhaoning, Cumming, Jared N, Liu, Xiaoxiang, Strickland, Corey, Mazzola, Robert D, Caldwell, John P, Leach, Prescott, Grzelak, Michael, Hyde, Lynn, Zhang, Qi, Terracina, Giuseppe, Zhang, Lili, Chen, Xia, Kuvelkar, Reshma, Kennedy, Matthew E, Favreau, Leonard, Cox, Kathleen, Orth, Peter, Buevich, Alexei, Voigt, Johannes, Wang, Hongwu, Kazakevich, Irina, McKittrick, Brian A, Greenlee, William, Parker, Eric M, Stamford, Andrew W

“…On the basis of our observation that the biaryl substituent of iminopyrimidinone 7 must be in a pseudoaxial conformation to occupy the contiguous S1–S3…”
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Discovery of a Tetrahydrobenzisoxazole Series of γ‑Secretase Modulators by Zhao, Zhiqiang, Pissarnitski, Dmitri A, Huang, Xianhai, Palani, Anandan, Zhu, Zhaoning, Greenlee, William J, Hyde, Lynn A, Song, Lixin, Terracina, Giuseppe, Zhang, Lili, Parker, Eric M

“…The design and synthesis of a new series of tetrahydrobenzisoxazoles as modulators of γ-secretase activity and their structure–activity relationship (SAR) will…”
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Discovery of an Orally Available, Brain Penetrant BACE1 Inhibitor That Affords Robust CNS Aβ Reduction by Stamford, Andrew W, Scott, Jack D, Li, Sarah W, Babu, Suresh, Tadesse, Dawit, Hunter, Rachael, Wu, Yusheng, Misiaszek, Jeffrey, Cumming, Jared N, Gilbert, Eric J, Huang, Chunli, McKittrick, Brian A, Hong, Liwu, Guo, Tao, Zhu, Zhaoning, Strickland, Corey, Orth, Peter, Voigt, Johannes H, Kennedy, Matthew E, Chen, Xia, Kuvelkar, Reshma, Hodgson, Robert, Hyde, Lynn A, Cox, Kathleen, Favreau, Leonard, Parker, Eric M, Greenlee, William J

“…Inhibition of BACE1 to prevent brain Aβ peptide formation is a potential disease-modifying approach to the treatment of Alzheimer’s disease. Despite over a…”
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Design and synthesis of water soluble β-aminosulfone analogues of SCH 900229 as γ-secretase inhibitors by Wu, Wen-Lian, Burnett, Duane A., Clader, John, Greenlee, William J., Jiang, Qin, Hyde, Lynn A., Del Vecchio, Robert A., Cohen-Williams, Mary E., Song, Lixin, Lee, Julie, Terracina, Giuseppe, Zhang, Qi, Nomeir, Amin, Parker, Eric M., Zhang, Lili

“…[Display omitted] In this paper we describe our strategy to improve the aqueous solubility of SCH 900229, a potent PS1-selective γ-secretase inhibitor for the…”
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Increased seizure threshold and severity in young transgenic CRND8 mice by Del Vecchio, Robert A., Gold, Lisa H., Novick, Steve J., Wong, Gwen, Hyde, Lynn A.

“…Reports suggest that Alzheimer’s disease (AD) patients show a high life-time prevalence of seizure-like disorders. The transgenic CRND8 (TgCRDN8) is a mouse…”
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Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors by Wu, Wen-Lian, Asberom, Theodros, Bara, Thomas, Bennett, Chad, Burnett, Duane A., Clader, John, Domalski, Martin, Greenlee, William J., Josien, Hubert, McBriar, Mark, Rajagopalan, Murali, Vicarel, Monica, Xu, Ruo, Hyde, Lynn A., Del Vecchio, Robert A., Cohen-Williams, Mary E., Song, Lixin, Lee, Julie, Terracina, Giuseppe, Zhang, Qi, Nomeir, Amin, Parker, Eric M., Zhang, Lili

“…An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (−)-1a (SCH 900229), a potent, PS1-selective…”
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Discovery of amide and heteroaryl isosteres as carbamate replacements in a series of orally active γ-secretase inhibitors by McBriar, Mark D., Clader, John W., Chu, Inhou, Del Vecchio, Robert A., Favreau, Leonard, Greenlee, William J., Hyde, Lynn A., Nomeir, Amin A., Parker, Eric M., Pissarnitski, Dmitri A., Song, Lixin, Zhang, Lili, Zhao, Zhiqiang

“…The design of amide and heteroaryl amide isosteres as replacements for the carbamate substructure in previously disclosed 2,6-disubstituted piperidine…”
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