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19 results on '"Färnegårdh, Mathias"'

2. Discovery of 3-Cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist

Author

Schnute, Mark E., primary, Wennerstål, Mattias, additional, Alley, Jennifer, additional, Bengtsson, Martin, additional, Blinn, James R., additional, Bolten, Charles W., additional, Braden, Timothy, additional, Bonn, Tomas, additional, Carlsson, Bo, additional, Caspers, Nicole, additional, Chen, Ming, additional, Choi, Chulho, additional, Collis, Leon P., additional, Crouse, Kimberly, additional, Färnegårdh, Mathias, additional, Fennell, Kimberly F., additional, Fish, Susan, additional, Flick, Andrew C., additional, Goos-Nilsson, Annika, additional, Gullberg, Hjalmar, additional, Harris, Peter K., additional, Heasley, Steven E., additional, Hegen, Martin, additional, Hromockyj, Alexander E., additional, Hu, Xiao, additional, Husman, Bolette, additional, Janosik, Tomasz, additional, Jones, Peter, additional, Kaila, Neelu, additional, Kallin, Elisabet, additional, Kauppi, Björn, additional, Kiefer, James R., additional, Knafels, John, additional, Koehler, Konrad, additional, Kruger, Lars, additional, Kurumbail, Ravi G., additional, Kyne, Robert E., additional, Li, Wei, additional, Löfstedt, Joakim, additional, Long, Scott A., additional, Menard, Carol A., additional, Mente, Scot, additional, Messing, Dean, additional, Meyers, Marvin J., additional, Napierata, Lee, additional, Nöteberg, Daniel, additional, Nuhant, Philippe, additional, Pelc, Matthew J., additional, Prinsen, Michael J., additional, Rhönnstad, Patrik, additional, Backström-Rydin, Eva, additional, Sandberg, Johnny, additional, Sandström, Maria, additional, Shah, Falgun, additional, Sjöberg, Maria, additional, Sundell, Aron, additional, Taylor, Alexandria P., additional, Thorarensen, Atli, additional, Trujillo, John I., additional, Trzupek, John D., additional, Unwalla, Ray, additional, Vajdos, Felix F., additional, Weinberg, Robin A., additional, Wood, David C., additional, Xing, Li, additional, Zamaratski, Edouard, additional, Zapf, Christoph W., additional, Zhao, Yajuan, additional, Wilhelmsson, Anna, additional, and Berstein, Gabriel, additional

Published
2018
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3. Thyroid Receptor Ligands. 6. A High Affinity “Direct Antagonist” Selective for the Thyroid Hormone Receptor

Author

Koehler, Konrad, primary, Gordon, Sandra, additional, Brandt, Peter, additional, Carlsson, Bo, additional, Bäcksbro-Saeidi, Anna, additional, Apelqvist, Theresa, additional, Agback, Peter, additional, Grover, Gary J., additional, Nelson, William, additional, Grynfarb, Marlena, additional, Färnegårdh, Mathias, additional, Rehnmark, Stefan, additional, and Malm, Johan, additional

Published
2006
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5. Thyroid receptor ligands. Part 5: Novel bicyclic agonist ligands selective for the thyroid hormone receptor β

Author

Garcia Collazo, Ana-Maria, primary, Koehler, Konrad F., additional, Garg, Neeraj, additional, Färnegårdh, Mathias, additional, Husman, Bolette, additional, Ye, Liu, additional, Ljunggren, Jan, additional, Mellström, Karin, additional, Sandberg, Johnny, additional, Grynfarb, Marlena, additional, Ahola, Harri, additional, and Malm, Johan, additional

Published
2006
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6. Liver-Selective Glucocorticoid Antagonists: A Novel Treatment for Type 2 Diabetes.

Author

von Geldern, Thomas W., primary, Tu, Noah, additional, Kym, Philip R., additional, Link, James T., additional, Jae, Hwan-Soo, additional, Lai, Chunqiu, additional, Apelqvist, Theresa, additional, Rhonnstad, Patrik, additional, Hagberg, Lars, additional, Koehler, Konrad, additional, Grynfarb, Marlena, additional, Goos-Nilsson, Annika, additional, Sandberg, Johnny, additional, Österlund, Marie, additional, Barkhem, Tomas, additional, Höglund, Marie, additional, Wang, Jiahong, additional, Fung, Steven, additional, Wilcox, Denise, additional, Nguyen, Phong, additional, Jakob, Clarissa, additional, Hutchins, Charles, additional, Färnegårdh, Mathias, additional, Kauppi, Björn, additional, Öhman, Lars, additional, and Jacobson, Peer B., additional

Published
2005
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8. Liver-Selective Glucocorticoid Antagonists: A Novel Treatment for Type 2 Diabetes

Author

von Geldern, Thomas W., primary, Tu, Noah, additional, Kym, Philip R., additional, Link, James T., additional, Jae, Hwan-Soo, additional, Lai, Chunqiu, additional, Apelqvist, Theresa, additional, Rhonnstad, Patrik, additional, Hagberg, Lars, additional, Koehler, Konrad, additional, Grynfarb, Marlena, additional, Goos-Nilsson, Annika, additional, Sandberg, Johnny, additional, Österlund, Marie, additional, Barkhem, Tomas, additional, Höglund, Marie, additional, Wang, Jiahong, additional, Fung, Steven, additional, Wilcox, Denise, additional, Nguyen, Phong, additional, Jakob, Clarissa, additional, Hutchins, Charles, additional, Färnegårdh, Mathias, additional, Kauppi, Björn, additional, Öhman, Lars, additional, and Jacobson, Peer B., additional

Published
2004
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9. Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta

Author

Hangeland, Jon J., primary, Doweyko, Arthur M., additional, Dejneka, Tamara, additional, Friends, Todd J., additional, Devasthale, Pratik, additional, Mellström, Karin, additional, Sandberg, Johnny, additional, Grynfarb, Marlena, additional, Sack, John S., additional, Einspahr, Howard, additional, Färnegårdh, Mathias, additional, Husman, Bolette, additional, Ljunggren, Jan, additional, Koehler, Konrad, additional, Sheppard, Cheryl, additional, Malm, Johan, additional, and Ryono, Denis E., additional

Published
2004
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11. The Three-dimensional Structures of Antagonistic and Agonistic Forms of the Glucocorticoid Receptor Ligand-binding Domain

Author

Kauppi, Björn, primary, Jakob, Clarissa, additional, Färnegårdh, Mathias, additional, Yang, Jie, additional, Ahola, Harri, additional, Alarcon, Maria, additional, Calles, Karin, additional, Engström, Owe, additional, Harlan, John, additional, Muchmore, Steven, additional, Ramqvist, Anna-Karin, additional, Thorell, Susanne, additional, Öhman, Lars, additional, Greer, Jonathan, additional, Gustafsson, Jan-Åke, additional, Carlstedt-Duke, Jan, additional, and Carlquist, Mats, additional

Published
2003
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16. Discovery of 3-Cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist.

Author

Schnute ME, Wennerstål M, Alley J, Bengtsson M, Blinn JR, Bolten CW, Braden T, Bonn T, Carlsson B, Caspers N, Chen M, Choi C, Collis LP, Crouse K, Färnegårdh M, Fennell KF, Fish S, Flick AC, Goos-Nilsson A, Gullberg H, Harris PK, Heasley SE, Hegen M, Hromockyj AE, Hu X, Husman B, Janosik T, Jones P, Kaila N, Kallin E, Kauppi B, Kiefer JR, Knafels J, Koehler K, Kruger L, Kurumbail RG, Kyne RE Jr, Li W, Löfstedt J, Long SA, Menard CA, Mente S, Messing D, Meyers MJ, Napierata L, Nöteberg D, Nuhant P, Pelc MJ, Prinsen MJ, Rhönnstad P, Backström-Rydin E, Sandberg J, Sandström M, Shah F, Sjöberg M, Sundell A, Taylor AP, Thorarensen A, Trujillo JI, Trzupek JD, Unwalla R, Vajdos FF, Weinberg RA, Wood DC, Xing L, Zamaratski E, Zapf CW, Zhao Y, Wilhelmsson A, and Berstein G

Subjects
Administration, Oral, Animals, Biological Availability, Drug Evaluation, Preclinical, Humans, Mice, Pyridines pharmacokinetics, Th17 Cells drug effects, Th17 Cells metabolism, Drug Design, Drug Inverse Agonism, Nuclear Receptor Subfamily 1, Group F, Member 3 agonists, Pyridines administration & dosage, Pyridines pharmacology
Abstract

The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, we identified a molecule displaying promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA and RORB receptor isoforms. Lead optimization to improve the potency and metabolic stability of this hit focused on two key design strategies, namely, iterative optimization driven by increasing lipophilic efficiency and structure-guided conformational restriction to achieve optimal ground state energetics and maximize receptor residence time. This approach successfully identified 3-cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide as a potent and selective RORC2 inverse agonist, demonstrating good metabolic stability, oral bioavailability, and the ability to reduce IL-17 levels and skin inflammation in a preclinical in vivo animal model upon oral administration.

Published
2018
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17. Thyroid receptor ligands. Part 5: novel bicyclic agonist ligands selective for the thyroid hormone receptor beta.

Author

Garcia Collazo AM, Koehler KF, Garg N, Färnegårdh M, Husman B, Ye L, Ljunggren J, Mellström K, Sandberg J, Grynfarb M, Ahola H, and Malm J

Subjects
Animals, Crystallography, X-Ray, Cyclization, Humans, Indoles metabolism, Inhibitory Concentration 50, Ligands, Molecular Structure, Rats, Substrate Specificity, Thyroid Hormone Receptors beta chemistry, Thyroxine chemical synthesis, Thyroxine chemistry, Indoles chemistry, Indoles pharmacology, Thyroid Hormone Receptors beta agonists, Thyroid Hormone Receptors beta metabolism
Abstract

Based on the examination of the crystal structure of rat TRbeta complexed with 3,5,3'-triiodo-l-thyronine (2) a novel TRbeta-selective indole derivative 6b was prepared and tested in vitro. This compound was found to be 14 times selective for TRbeta over TRalpha in binding and its beta-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRalpha and TRbeta.

Published
2006
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18. The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands.

Author

Färnegårdh M, Bonn T, Sun S, Ljunggren J, Ahola H, Wilhelmsson A, Gustafsson JA, and Carlquist M

Subjects
Alanine chemistry, Binding Sites, Cholesterol metabolism, DNA-Binding Proteins, Dimerization, Electrons, Escherichia coli metabolism, Histidine chemistry, Humans, Ligands, Liver X Receptors, Models, Chemical, Models, Molecular, Models, Statistical, Orphan Nuclear Receptors, Protein Binding, Protein Conformation, Protein Isoforms, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear metabolism, Transcription Factors metabolism, Transcription, Genetic, X-Rays, Receptors, Cytoplasmic and Nuclear chemistry
Abstract

The structures of the liver X receptor LXRbeta (NR1H2) have been determined in complexes with two synthetic ligands, T0901317 and GW3965, to 2.1 and 2.4 A, respectively. Together with its isoform LXRalpha (NR1H3) it regulates target genes involved in metabolism and transport of cholesterol and fatty acids. The two LXRbeta structures reveal a flexible ligand-binding pocket that can adjust to accommodate fundamentally different ligands. The ligand-binding pocket is hydrophobic but with polar or charged residues at the two ends of the cavity. T0901317 takes advantage of this by binding to His-435 close to H12 while GW3965 orients itself with its charged group in the opposite direction. Both ligands induce a fixed "agonist conformation" of helix H12 (also called the AF-2 domain), resulting in a transcriptionally active receptor.

Published
2003
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19. Expression and preliminary crystallographic studies of R1E, the large subunit of ribonucleotide reductase from Salmonella typhimurium.

Author

Uppsten M, Färnegårdh M, Jordan A, Ramaswamy S, and Uhlin U

Subjects
Crystallization, Genes, Bacterial genetics, Ribonucleotide Reductases genetics, Ribonucleotide Reductases metabolism, Salmonella typhimurium genetics, Salmonella typhimurium metabolism, X-Ray Diffraction, Ribonucleotide Reductases chemistry, Salmonella typhimurium chemistry
Abstract

The nrdE gene product R1E, the large subunit of the class 1b Salmonella typhimurium ribonucleotide reductase, has been overexpressed, purified and crystallized. Initially, the protein crystallized in two orthorhombic space groups, C222(1) and P2(1)2(1)2, using tartrate and PEG 6000 as precipitants, respectively. Better diffracting crystals belonging to the tetrahedral space group P4(3)2(1)2 were obtained using sodium malonate as precipitant. The P4(3)2(1)2 crystals could only be obtained after seeding from a drop containing C222(1) crystals grown in sodium tartrate. Thus, streak-seeding resulted in crystals of a supergroup to C222(1). Data to 2.8 A resolution have been collected on the P4(3)2(1)2 crystals which contained one R1E subunit in the asymmetric unit.

Published
2003
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