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Your search keyword '"Joe Metzger"' showing total 3 results
Start Over Author "Joe Metzger" Topic biology
3 results on '"Joe Metzger"'

1. Discovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys

Author

Chris J. van Koppen, Scott B. Hoyt, Gino Salituro, Elaine Tung, Jim Tata, Joe Clemas, Mark Rosenbach, Jack Gibson, Daphne Szeto, Wei Tang, Andreas Verras, Lee-Yuh Pai, Ning Ren, Carrie Ann Maxwell, Joe Metzger, Jose Castro-Perez, Qing Chen, Lina Yin, Daniel R. McMasters, Yusheng Xiong, Rolf W. Hartmann, Mary Struthers, Gui-Bai Liang, Charlene Bopp, Xiuying Ma, Gaochao Zhou, Richard Hajdu, Tom Wisniewski, Mike E. Lassman, Nicole Buist, Clare London, Andrea Sok, Gail Forrest, Sloan Stribling, Theresa McLaughlin, Qingzhong Hu, Tian-Quan Cai, and Whitney Lane Petrilli

Subjects
Aldosterone synthase, medicine.medical_specialty, Aldosterone, Organic Chemistry, Triazole, Hit to lead, Biology, Pharmacology, Biochemistry, chemistry.chemical_compound, Endocrinology, chemistry, Pharmacokinetics, In vivo, Pharmacodynamics, Internal medicine, Drug Discovery, medicine, biology.protein, Cortisol level
Abstract

Hit-to-lead efforts resulted in the discovery of compound 19, a potent CYP11B2 inhibitor that displays high selectivity vs related CYPs, good pharmacokinetic properties in rat and rhesus, and lead-like physical properties. In a rhesus pharmacodynamic model, compound 19 displays robust, dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.

Published
2015

2. Discovery of Benzimidazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys

Author

Daphne Szeto, Doris F. Cully, Scott B. Hoyt, Ning Ren, Elaine Tung, Charlene Bopp, Jack Gibson, Gino Salituro, Clare London, Jiaqiang Cai, Amjad Ali, Qing Chen, Andrea Sok, Simone Belshaw, Carrie Ann Maxwell, Mark Rosenbach, Gaochao Zhou, Gail Forrest, Tian-Quan Cai, Daniel R. McMasters, Lee-Yuh Pai, Nelo R. Rivera, Sloan Stribling, Emma Carswell, Richard Hajdu, Robinson John E, Andrew J. Cooke, Jeff Kuethe, Tom Wisniewski, Joe Metzger, Thomas R. Clarkson, Gui-Bai Liang, Mary Struthers, Jim Tata, Mike E. Lassman, Lindsay Brown, Wei Tang, Theresa McLaughlin, Xiuying Ma, Nicole Buist, Kun Liu, Joe Clemas, D. Jonathan Bennett, Andreas Verras, Min K. Park, Yusheng Xiong, John Maclean, and Jose Castro-Perez

Subjects
Aldosterone synthase, Benzimidazole, medicine.medical_specialty, Aldosterone, Organic Chemistry, High selectivity, Biology, Pharmacology, Biochemistry, chemistry.chemical_compound, Endocrinology, chemistry, Pharmacokinetics, In vivo, Internal medicine, Pharmacodynamics, Drug Discovery, medicine, biology.protein, Cortisol level
Abstract

We report the discovery of a benzimidazole series of CYP11B2 inhibitors. Hit-to-lead and lead optimization studies identified compounds such as 32, which displays potent CYP11B2 inhibition, high selectivity versus related CYP targets, and good pharmacokinetic properties in rat and rhesus. In a rhesus pharmacodynamic model, 32 produces dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.

Published
2015

3. [Untitled]

Author

Donald J. Marsh, D. E. Macintyre, Xiao-Ming Guan, Michael J. Forrest, Easter G. Frazier, Airu S. Chen, Theodore N. Mellin, Ramon E. Camacho, Hong Yu, Jill K. Fisher, Van der Ploeg Lh, Joe Metzger, Alison M. Strack, Myrna E. Trumbauer, Howard Y. Chen, and Shobhna Gopal-Truter

Subjects
Agonist, medicine.medical_specialty, medicine.drug_class, digestive, oral, and skin physiology, Melanotan II, Biology, medicine.disease, Melanocortin 4 receptor, Endocrinology, Hormone receptor, Internal medicine, Knockout mouse, Basal metabolic rate, Genetics, medicine, Hyperinsulinemia, Animal Science and Zoology, Receptor, Agronomy and Crop Science, Biotechnology, medicine.drug
Abstract

We evaluated the role of the melanocortin-4 receptor (MC-4R) in the control of metabolic rate and food intake in mice. Intraperitoneal administration of the non-selective MC-R agonist melanotan II (MT-II; a cyclic heptapeptide) increases metabolic rate in wildtype mice, while MC-4R knockout mice are insensitive to the effects of MT-II on metabolic rate. MC-4R knockout mice are also insensitive to the effects of MT-II on reducing food intake. We conclude that MC-4R can mediate control of both metabolic rate and food intake in mice. We infer that a role for MC-3R in mediating the acute effects of MT-II on basal metabolic rate and food intake in wildtype mice seems limited.

Published
2000

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