Zobrazeno 1 - 10
of 14
pro vyhledávání: '"Paul Stetsko"'
Autor:
Emily Luk, Karen E. Parrish, Yue-Zhong Shu, Anwar Murtaza, Yongnian Sun, Jinwen Huang, Robert M. Borzilleri, Paul Stetsko, Mary Ellen Cvijic, Jonathan G. Pabalan, Lihong Cheng, Zheng Yang, Jesse Swanson, James R. Burke, Tatyana Zvyaga, James Smalley, Karen A. Augustine
Publikováno v:
Biopharmaceutics & Drug Disposition. 42:137-149
Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that has a wide array of biological effects. For decades, tumor biology implicated TGF-β as an attractive therapeutic target due to its immunosuppressive effects. Toward this end, mu
Autor:
Neil Flynn, Mary Jane Cullen, Hongwei Zhang, Wei Wang, Susan Glick, Lisa Zhang, Jeffrey A. Robl, Pratik Devasthale, Andres S. Hernandez, Christian Caporuscio, Brian J. Murphy, Suzanne Rooney, Ning Huang, Mary Ann Pelleymounter, Kenneth W. Rohrbach, Kishore Renduchintala, Anthony V. Azzara, Helen E. Godonis, Yi-Xin Li, Radhakrishnan Sridhar, Michael Thomas, Susan Harvey, Paul Stetsko, Mary F. Grubb, Chris Freeden, Fang Moore, Christine Huang, James Devenny, Daniel Longhi, William N. Washburn
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 25:2793-2799
Our investigation of the structure–activity and structure–liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can i
Autor:
Atsu Apedo, Pancras C. Wong, Olafur S. Gudmundsson, Nathalie Toussaint, Yiming Wu, Timothy W. Harper, Silvi A. Chacko, Leon M. Smith, Baomin Xin, Dietmar A. Seiffert, Steven Sheriff, Ruth R. Wexler, William R. Ewing, Jeffrery M. Bozarth, Mimi L. Quan, Zhen Lou, Earl J. Crain, Brad D. Maxwell, Joanna J. Zheng, Arvind Mathur, Paul Stetsko, Joseph E. Myers, Donald J. P. Pinto, Michael J. Orwat, Karen A. Rossi, Patrick Y.S. Lam, Xiaoping Hou, Joseph M. Luettgen, Huiping Zhang
Publikováno v:
Journal of medicinal chemistry. 60(23)
Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Precli
Autor:
Jeffrey A. Robl, Guohua Zhao, Joel C. Barrish, Bei Wang, Brad D. Maxwell, Christian Caporuscio, Hongwei Zhang, James Devenny, Mary F. Grubb, Zhenghua Wang, Suzanne Rooney, James Mignone, Lisa Zhang, Brian J. Murphy, Wei Wang, Daniel Longhi, William N. Washburn, Kenneth W. Rohrbach, Evan B. Janovitz, Mark C. Manfredi, Mary Ann Pelleymounter, Michael Thomas, Hong Yang, Paul Stetsko, Saleem Ahmad, Atsu Apedo, Mary Jane Cullen, Brian Gemzik, Ning Huang, Chris Freeden, Susan Harvey, Anthony V. Azzara, Khehyong Ngu, Christine Huang, Rulin Zhao, Susan Glick, Neil Flynn, Pratik Devasthale, Andres S. Hernandez, Helen E. Godonis
Publikováno v:
Journal of Medicinal Chemistry. 57:7509-7522
Identification of MCHR1 antagonists with a preclinical safety profile to support clinical evaluation as antiobesity agents has been a challenge. Our finding that a basic moiety is not required for MCHR1 antagonists to achieve high affinity allowed us
Autor:
Kenneth E. Carlson, Olafur S. Gudmundsson, Bruce A. Ellsworth, Philip M. Sher, Susan Harvey, Eva Zuvich, Michael Thomas, William J. Keim, Gang Wu, Helen E. Godonis, Paul Stetsko, Brian J. Murphy, Richard B. Sulsky, Guixue Yu, William R. Ewing, Mary Jane Cullen, Mary Ann Pelleymounter, Doree F. Sitkoff, Susan Johnghar, Zhengxiang Gu, Ximao Wu, James Devenny, Rose Ann F Baska, Asoka Ranasinghe, Ning Lee, Kamelia Behnia, Anthony V. Azzara, Kenneth W. Rohrbach, Gerry Everlof, Liya Kang, Natesan Murugesan, Yeheng Zhu, Yifan Yang
Publikováno v:
Journal of Medicinal Chemistry. 56:9586-9600
Several strategies have been employed to reduce the long in vivo half-life of our lead CB1 antagonist, triazolopyridazinone 3, to differentiate the pharmacokinetic profile versus the lead clinical compounds. An in vitro and in vivo clearance data set
Autor:
Michael L. Doyle, Preeti Sejwal, Jun Dai, Aaron P. Yamniuk, Noah Ditto, Mehul Patel, Paul Stetsko
Publikováno v:
Journal of Pharmaceutical Sciences. 102:2424-2439
Aggregation propensity is a critical attribute of protein therapeutics that can influence production, manufacturing, delivery, and potential activity and safety (immunogenicity). It is therefore imperative to select molecules with low aggregation pro
Autor:
Petia Shipkova, James P. Wojciechowski, Punit Marathe, Robert Paul Brigance, Kamelia Behnia, Andrew Henwood, Georgia Cornelius, Susan Johnghar, Jian Wang, A. David Rodrigues, Paul Stetsko, W. Griffith Humphreys, William N. Washburn
Publikováno v:
Chemical Research in Toxicology. 24:905-912
The development of compounds with the potential for genotoxicity poses significant safety risks as well as risks of attrition. Although genotoxicity evaluation of the parent molecule is routine and reasonably predictive, assessing the risk of commerc
Autor:
Brian J. Murphy, James Devenny, Suzanne Rooney, Jagannath Selvaraj, James Mignone, Susan Glick, Sridhar Radhakrishnan, Helen E. Godonis, Neil Flynn, Rajesh Kuppusamy, Jayanthi Dhanapal, Mary Ann Pelleymounter, Chris Freeden, Pratik Devasthale, Daniel Longhi, William N. Washburn, Ning Huang, Christian Caporuscio, Mary F. Grubb, Paul Stetsko, Kenneth W. Rohrbach, Mary Jane Cullen, Christine Huang, Wei Wang, Susan Harvey, Hongwei Zhang, Lisa Zhang, Michael Thomas, Jeffrey A. Robl, Kishore Renduchintala, Anthony V. Azzara
Publikováno v:
Bioorganicmedicinal chemistry letters. 25(20)
Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 Ki=1.8 nM), demonstrated
Publikováno v:
Pharmaceutical research. 32(8)
An unknown UV 280 nm absorbing peak was observed by SEC for protein stability samples formulated in L-histidine during a stress stability study. Understanding the source would enhance the confidence in the SEC results. We identified the unknown peak,
Autor:
Munir A. Hussain, Ronald L. Smith, Doris A. Wall, Paul Moench, Christopher L. Heran, Neil Mathias, Paul Stetsko
Publikováno v:
Journal of Pharmaceutical Sciences. 92:1735-1738