Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care.

Autor: Kathleen M Gillooly, Claudine Pulicicchio, Mark A Pattoli, Lihong Cheng, Stacey Skala, Elizabeth M Heimrich, Kim W McIntyre, Tracy L Taylor, Daniel W Kukral, Shailesh Dudhgaonkar, Jignesh Nagar, Dana Banas, Scott H Watterson, Joseph A Tino, Aberra Fura, James R Burke

Publikováno v: PLoS ONE, Vol 12, Iss 7, p e0181782 (2017)

Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune disorders. BMS-986142 is a potent and highly selective reversible small molecule inhibitor o

Externí odkaz: https://doaj.org/article/5e3c5932a267466f99bceb70bcad96d8

Evaluation of BMS-986142, a reversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis:a phase 2, randomised, double-blind, dose-ranging, placebo-controlled, adaptive design study

Autor: Philip G Conaghan, Miroslawa Nowak, Shuyan Du, Yi Luo, Jessica Landis, Chahin Pachai, Aberra Fura, Ian M Catlett, Dennis M Grasela, Mikkel Østergaard

Publikováno v: Conaghan, P G, Nowak, M, Du, S, Luo, Y, Landis, J, Pachai, C, Fura, A, Catlett, I M, Grasela, D M & Østergaard, M 2023, ' Evaluation of BMS-986142, a reversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis : a phase 2, randomised, double-blind, dose-ranging, placebo-controlled, adaptive design study ', The Lancet Rheumatology, vol. 5, no. 5, pp. e263-e273 . https://doi.org/10.1016/S2665-9913(23)00089-9

Background: Bruton's tyrosine kinase (BTK) is a promising biological target for rheumatoid arthritis treatment. This study examined safety, efficacy, and pharmacokinetics of BMS-986142, an oral, reversible BTK inhibitor. The aim was to compare the ef

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c7c594bab974f6871b2a89b39bd4f94
https://curis.ku.dk/portal/da/publications/evaluation-of-bms986142-a-reversible-brutons-tyrosine-kinase-inhibitor-for-the-treatment-of-rheumatoid-arthritis(1288124e-252c-44f0-b4d6-eceb14a65ff5).html

Azatricyclic Inverse Agonists of RORγt That Demonstrate Efficacy in Models of Rheumatoid Arthritis and Psoriasis

Autor: Aberra Fura, Shiuhang Yip, Georgia Cornelius, Hai-Yun Xiao, Qingjie Liu, Sha Li, Ning Li, Nicholas A. Meanwell, Shailesh Dudhgaonkar, Max Ruzanov, Jenny Xie, Zili Xiao, Purnima Khandelwal, Carolyn A. Weigelt, David J. Shuster, Dauh-Rurng Wu, T. G. Murali Dhar, Tara Sherry, Yang Michael G, Kevin Stefanski, Jignesh Nagar, Rex Denton, Qihong Zhao, Peng Li, Silvi A. Chacko, Arun Govindarajan, Robert M. Borzilleri, John S. Sack, Yeheng Zhu, Yunling Song, Dawn Sun, Anjuman Rudra, Mary T. Obermeier, Jinhong Wang, Douglas G. Batt, Venkata Murali

Publikováno v: ACS Med Chem Lett

[Image: see text] Structure–activity relationship studies directed toward the replacement of the fused phenyl ring of the lead hexahydrobenzoindole RORγt inverse agonist series represented by 1 with heterocyclic moieties led to the identification

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d3296d470de82e26da82050921646783
https://doi.org/10.1021/acsmedchemlett.1c00112

Population Pharmacokinetic Analysis of BMS‐986166, a Novel Selective Sphingosine‐1‐Phosphate‐1 Receptor Modulator, and Exposure‐Response Assessment of Lymphocyte Counts and Heart Rate in Healthy Participants

Autor: Kuan‐ju Lin, Shalabh Singhal, Shenita Basdeo, Huadong Sun, John Throup, Hannah Huang, Aberra Fura, Ang Liu, Sebastien Bihorel, Ihab G. Girgis, Elizabeth Ludwig, Diane E. Shevell, Jenny Xie, Santanu Dutta

Publikováno v: Clinical Pharmacology in Drug Development

Sphingosine‐1‐phosphate (S1P) binding to the S1P‐1 receptor (S1P1R) controls the egress of lymphocytes from lymphoid organs and targets modulation of immune responses in autoimmune diseases. Pharmacologic modulation of S1P receptors has been li

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bede4651619c4a35110c650d35f35e3
http://europepmc.org/articles/PMC7821288

Driving Potency with Rotationally Stable Atropisomers: Discovery of Pyridopyrimidinedione-Carbazole Inhibitors of BTK

Autor: Soo S. Ko, James Kempson, Yingru Zhang, Tracy L. Taylor, Kim W. McIntyre, James R. Burke, Luisa Salter-Cid, Shiuhang Yip, Celia D’Arienzo, Aberra Fura, Stacey Skala, Joseph A. Tino, Jun Dai, Chunlei Wang, Joel C. Barrish, Michael Galella, Kathleen M. Gillooly, Bei Wang, Dauh-Rurng Wu, Lorell Discenza, Xiaoping Hou, Arvind Mathur, Richard Rampulla, Dawn Sun, Scott H. Watterson, Mary T. Obermeier, Percy H. Carter, Mark A. Pattoli, Anurag S. Srivastava, Lihong Cheng, Rulin Zhao, Peng Li, Claudine Pulicicchio, Joseph Pawluczyk, Rodney Vickery

Publikováno v: ACS Med Chem Lett

[Image: see text] Bruton’s tyrosine kinase (BTK) has been shown to play a key role in the pathogenesis of autoimmunity. Therefore, the inhibition of the kinase activity of BTK with a small molecule inhibitor could offer a breakthrough in the clinic

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26e4c1b44296b4486a9db31077574eba
https://pubmed.ncbi.nlm.nih.gov/33214829