Zobrazeno 1 - 10
of 35
pro vyhledávání: '"Dennis Colussi"'
Autor:
Georgia B. McGaughey, Samuel L. Graham, M. Katharine Holloway, Sharie J. Haugabook, Paul Zuck, Abigail Wolfe, Katherine Tugasheva, Sanjeev Munshi, Joseph P. Vacca, Timothy Allison, Thomas G. Steele, Alessia Petrocchi, Dennis Colussi, Shawn J. Stachel
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 22:240-244
We have developed a novel series of pyrrolidine derived BACE-1 inhibitors. The potency of the weak initial lead structure was enhanced using library-based SAR methods. The series was then further advanced by rational design while maintaining a minima
Autor:
Beth Pietrak, Hemaka A. Rajapakse, Dennis Colussi, Paul Zuck, Hong Zhu, Kristen L.G. Jones, Adam J. Simon, Samuel L. Graham, Shawn J. Stachel, M. Katharine Holloway, Diane M. Rush, Joseph P. Vacca, Amy S. Espeseth, Tim J. Allison, Ming-Tain Lai, Craig A. Coburn, Abigail Wolfe, Sanjeev Munshi
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 19:2977-2980
We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile,
Autor:
John Swestock, Ming Tain Lai, Shaun R. Stauffer, Sanjeev Munshi, Georgia B. McGaughey, Joseph P. Vacca, Marie A. Holahan, Keith P. Moore, Dennis Colussi, Hemaka A. Rajapakse, Mathew G. Stanton, Maria S. Michener, Jacquelynn J. Cook, Allison R. Gregro, Philippe G. Nantermet, Sethu Sankaranarayanan, James C. Barrow, Harold G. Selnick, Adam J. Simon, Melissa A. Steinbeiser, Samuel L. Graham
Publikováno v:
ChemMedChem. 4:37-40
Autor:
Amy S. Espeseth, Ivory D. Hills, Shawn J. Stachel, Thomas G. Steele, Georgia B. McGaughey, Sharie J. Haugabook, Samuel L. Graham, Paul Zuck, Timothy Allison, Pablo De Leon, Ashley Nomland, Katherine Tugusheva, Dennis Colussi
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 19:17-20
A small molecule inhibitor of beta-secretase with a unique binding mode has been developed. Crystallographic determination of the enzyme-inhibitor complex shows the catalytic aspartate residues in the active site are not engaged in inhibitor binding.
Autor:
Janet Lineberger, Matthew G. Stanton, Amy S. Espeseth, Beth Pietrak, Min Xu, Katherine Tugusheva, Harold G. Selnick, Dennis Colussi, Guy R. Seabrook, John Swestock, Jason Kahana, Ming-Chih Crouthamel, Viswanath Devanarayan, Keala X. Tyler, Guoxin Wu, Daria J. Hazuda, Shaun R. Stauffer, Joan D. Ellis, Marie A. Holahan, Joseph P. Vacca, Philippe G. Nantermet, Melissa A. Steinbeiser, Georgia B. McGaughey, Eric A. Price, Jerome Hochman, Hemaka A. Rajapakse, Sethu Sankaranarayanan, Adam J. Simon, Samuel L. Graham, Keith P. Moore, M. Katharine Holloway, Ming-Tain Lai, Lixia Jin, Adam Gates, Xiao-Ping Shi, Jacky Wong, Jacquelynn J. Cook, Allison R. Gregro
Publikováno v:
Journal of Pharmacology and Experimental Therapeutics. 328:131-140
beta-Site amyloid precursor protein (APP)-cleaving enzyme (BACE) 1 cleavage of amyloid precursor protein is an essential step in the generation of the potentially neurotoxic and amyloidogenic A beta 42 peptides in Alzheimer's disease. Although previo
Autor:
Kenneth E. Rittle, Dorothy Levorse, James C. Barrow, Eric A. Price, Katherine Tugusheva, Ming Tain Lai, Abigail Wolfe, Dennis Colussi, Paul Zuck, Shaun R. Stauffer, Adam J. Simon, Samuel L. Graham, M. Katharine Holloway, Zhi Qiang Yang, Georgia B. McGaughey, Amy S. Espeseth, Phung L. Ngo, Beth Pietrak, Min Xu, Qian Huang, Joseph P. Vacca, Sethu Sankaranarayanan, Daria J. Hazuda, Sanjeev Munshi, Harold G. Selnick
Publikováno v:
Journal of Medicinal Chemistry. 51:6259-6262
A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding where
Autor:
Samuel L. Graham, Amy S. Espeseth, Kenneth E. Rittle, Katherine Tugusheva, Dennis Colussi, Phung L. Ngo, Ming Tain Lai, Georgia B. McGaughey, Steven M. Pitzenberger, Harold G. Selnick, Qian Huang, Joseph P. Vacca, Adam J. Simon, Sanjeev Munshi, James C. Barrow
Publikováno v:
ChemMedChem. 2:995-999
Autor:
Georgia B. McGaughey, Ming-Tain Lai, Hemaka A. Rajapakse, Sanjeev Munshi, Beth Pietrak, Philippe G. Nantermet, Shaun R. Stauffer, Samuel L. Graham, M. Katharine Holloway, Dennis Colussi, Harold G. Selnick
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 17:1117-1121
BACE-1 is a flexible enzyme with experimentally determined motion in the flap region, the catalytic aspartates, and the 10s loop. Four in-house crystallographically determined complexes of tertiary carbinamine inhibitors revealed 10s loop motion in t
Autor:
Lixia Jin, Shawn J. Stachel, Jacquelynn J. Cook, I. W. Chen, Marie A. Holahan, Steven M. Pitzenberger, Harold G. Selnick, Lou Anne Neilson, Debra S. Perlow, Craig A. Coburn, Melissa Egbertson, Beth Pietrak, John Swestock, Wenjin Yang, Georgia B. McGaughey, Ming Tain Lai, Maria Stranieri-Michener, James C. Barrow, Melody Mcwherter, Shaun R. Stauffer, Joseph P. Vacca, Shari Haugabook, Adam J. Simon, Samuel L. Graham, M. Katharine Holloway, Sethu Sankaranarayanan, Sanjeev Munshi, Zhi-Qiang Yang, Timothy Allison, Bruce Fahr, Katherine Tugusheva, Dennis Colussi
Publikováno v:
Bioorganicmedicinal chemistry letters. 25(21)
The IC50 of a beta-secretase (BACE-1) lead compound was improved ∼200-fold from 11 μM to 55 nM through the addition of a single methyl group. Computational chemistry, small molecule NMR, and protein crystallography capabilities were used to compar
Autor:
Guoxin Wu, Shi-Shan Mao, Steven S. Carroll, Dennis Colussi, Marie A. Holahan, Carolyn Bailey, Jacquelynn J. Cook
Publikováno v:
Blood Coagulation & Fibrinolysis. 16:407-415
To investigate the importance of thrombin activatable fibrinolysis inhibitor (TAFI) in the stabilization of plasma clots, we have compared fibrinolysis in TAFI-deficient (KO) and wild-type (WT) littermate mice. TAFI-deficient mice were previously gen