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Your search keyword '"Mackman, Richard"' showing total 7 results
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7 results on '"Mackman, Richard"'

1. Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys.

Author

Mackman, Richard L., Kalla, Rao V., Babusis, Darius, Pitts, Jared, Barrett, Kimberly T., Chun, Kwon, Du Pont, Venice, Rodriguez, Lauren, Moshiri, Jasmine, Xu, Yili, Lee, Michael, Lee, Gary, Bleier, Blake, Nguyen, Anh-Quan, O'Keefe, B. Michael, Ambrosi, Andrea, Cook, Meredith, Yu, Joy, Dempah, Kassibla Elodie, and Bunyan, Elaine

Published
2023
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3. Contribution of multicentered short hydrogen bond arrays to potency of active site-directed serine protease inhibitors

Author

Katz, Bradley A., Spencer, Jeffery R., Elrod, Kyle, Luong, Christine, and Mackman, Richard L.

Subjects
Protease inhibitors -- Research, Hydrogen-ion concentration -- Chemical properties, Hydrogen bonding -- Research, Chemistry
Abstract

The pH dependencies of the potencies and of the bound structures of two inhibitor that form multicentered short hydrogen bond arrays at the active sites of tryspin, thrombin and urokinase type plasminogen activator over certain ranges of pH is described. Comparison of structure and Ki values of tryspin complexes at pH values where the multicentered short hydrogen bond arrays mediating inhibitor binding are present or absent indicate that these arrays have a minor effect on inhibitor potency.

Published
2002

4. Discovery of GS-9688 (Selgantolimod) as a Potent and Selective Oral Toll-Like Receptor 8 Agonist for the Treatment of Chronic Hepatitis B.

Author

Mackman, Richard L., Mish, Michael, Chin, Gregory, Perry, Jason K., Appleby, Todd, Aktoudianakis, Vangelis, Metobo, Sammy, Pyun, Peter, Niu, Congrong, Daffis, Stephane, Yu, Helen, Zheng, Jim, Villasenor, Armando G., Zablocki, Jeff, Chamberlain, Jason, Jin, Haolun, Lee, Gary, Suekawa-Pirrone, Kimberley, Santos, Rex, and Delaney IV, William E.

Published
2020
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5. Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle.

Author

Mackman, Richard L., Steadman, Victoria A., Dean, David K., Jansa, Petr, Poullennec, Karine G., Appleby, Todd, Austin, Carol, Blakemore, Caroline A., Cai, Ruby, Cannizzaro, Carina, Chin, Gregory, Chiva, Jean-Yves C., Dunbar, Neil A., Fliri, Hans, Highton, Adrian J., Hui, Hon, Ji, Mingzhe, Jin, Haolun, Karki, Kapil, and Keats, Andrew J.

Published
2018
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7. Discovery of an Oral RespiratorySyncytial Virus (RSV)Fusion Inhibitor (GS-5806) and Clinical Proof of Concept in a HumanRSV Challenge Study.

Author

Mackman, Richard L., Sangi, Michael, Sperandio, David, Parrish, Jay P., Eisenberg, Eugene, Perron, Michel, Hon Hui, Lijun Zhang, Siegel, Dustin, Hai Yang, Saunders, Oliver, Boojamra, Constantine, Lee, Gary, Samuel, Dharmaraj, Babaoglu, Kerim, Carey, Anne, Gilbert, Brian E., Piedra, Pedro A., Strickley, Robert, and Iwata, Quynh

Subjects
*RESPIRATORY syncytial virus infections, *VIRUS inhibitors, *DRUG development, *BIOAVAILABILITY, *DRUG use testing, *PYRIMIDINES, *PYRROLIDINE, *THERAPEUTICS
Abstract

GS-5806is a novel, orally bioavailable RSV fusion inhibitor discoveredfollowing a lead optimization campaign on a screening hit. The oralabsorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, andphysicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. A mean EC50= 0.43 nM was found toward a panel of 75 RSV A and B clinical isolatesand dose-dependent antiviral efficacy in the cotton rat model of RSVinfection. Oral bioavailability in preclinical species ranged from46 to 100%, with evidence of efficient penetration into lung tissue.In healthy human volunteers experimentally infected with RSV, a potentantiviral effect was observed with a mean 4.2 log10reductionin peak viral load and a significant reduction in disease severitycompared to placebo. In conclusion, a potent, once daily, oral RSVfusion inhibitor with the potential to treat RSV infection in infantsand adults is reported. [ABSTRACT FROM AUTHOR]

Published
2015
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