NBI-921352, a first-in-class, NaV1.6 selective, sodium channel inhibitor that prevents seizures in Scn8a gain-of-function mice, and wild-type mice and rats

Autor: JP Johnson, Thilo Focken, Kuldip Khakh, Parisa Karimi Tari, Celine Dube, Samuel J Goodchild, Jean-Christophe Andrez, Girish Bankar, David Bogucki, Kristen Burford, Elaine Chang, Sultan Chowdhury, Richard Dean, Gina de Boer, Shannon Decker, Christoph Dehnhardt, Mandy Feng, Wei Gong, Michael Grimwood, Abid Hasan, Angela Hussainkhel, Qi Jia, Stephanie Lee, Jenny Li, Sophia Lin, Andrea Lindgren, Verner Lofstrand, Janette Mezeyova, Rostam Namdari, Karen Nelkenbrecher, Noah Gregory Shuart, Luis Sojo, Shaoyi Sun, Matthew Taron, Matthew Waldbrook, Diana Weeratunge, Steven Wesolowski, Aaron Williams, Michael Wilson, Zhiwei Xie, Rhena Yoo, Clint Young, Alla Zenova, Wei Zhang, Alison J Cutts, Robin P Sherrington, Simon N Pimstone, Raymond Winquist, Charles J Cohen, James R Empfield

Publikováno v: eLife, Vol 11 (2022)

NBI-921352 (formerly XEN901) is a novel sodium channel inhibitor designed to specifically target NaV1.6 channels. Such a molecule provides a precision-medicine approach to target SCN8A-related epilepsy syndromes (SCN8A-RES), where gain-of-function (G

Externí odkaz: https://doaj.org/article/ff1c4ccf767e411f85c1b12a0db8fe55

Identification of aryl sulfonamides as novel and potent inhibitors of Na

Autor: Shaoyi, Sun, Qi, Jia, Alla Y, Zenova, Sophia, Lin, Angela, Hussainkhel, Janette, Mezeyova, Elaine, Chang, Samuel J, Goodchild, Zhiwei, Xie, Andrea, Lindgren, Gina, de Boer, Rainbow, Kwan, Kuldip, Khakh, Luis, Sojo, Paul, Bichler, J P, Johnson, James R, Empfield, Charles J, Cohen, Christoph M, Dehnhardt, Richard, Dean

Publikováno v: Bioorganicmedicinal chemistry letters. 45

We describe the synthesis and biological evaluation of a series of novel aryl sulfonamides that exhibit potent inhibition of Na

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::72ffd93fb821803255bea0175c7110a5
https://pubmed.ncbi.nlm.nih.gov/34044121

Progress in Understanding and Treating SCN2A-Mediated Disorders

Autor: Dheeraj Malhotra, Raphael Bernier, Stephen Sanders, James R. Empfield, Kevin J. Bender, Geoffrey S. Pitt, Arthur J. Campbell, Wendy K. Chung, William A. Catterall, Rikke S. Møller, Alfred L. George, Joerg F. Hipp, Jennifer Tjernagel, John Millichap, Evangelos Kiskinis, Florence F. Wagner, Cora Taylor, Dennis Lal, John E. Spiro, Leah F. Schust, Jeffrey R. Cottrell, Thomas S. Otis, Angie L. Auldridge, Steven Petrou, Omar Khwaja

Publikováno v: Trends in neurosciences, vol 41, iss 7
Sanders, S J, Campbell, A J, Cottrell, J R, Moller, R S, Wagner, F F, Auldridge, A L, Bernier, R A, Catterall, W A, Chung, W K, Empfield, J R, George, A L, Hipp, J F, Khwaja, O, Kiskinis, E, Lal, D, Malhotra, D, Millichap, J J, Otis, T S, Petrou, S, Pitt, G, Schust, L F, Taylor, C M, Tjernagel, J, Spiro, J E & Bender, K J 2018, ' Progress in Understanding and Treating SCN2A-Mediated Disorders ', Trends in Neurosciences, vol. 41, no. 7, pp. 442-456 . https://doi.org/10.1016/j.tins.2018.03.011

Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functiona

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::368f22a1be36996d1c034e8fc9066f8a
https://escholarship.org/uc/item/1b1284bd

Reducing Drug Attrition

Autor: James R. Empfield, Michael P Clark

Publikováno v: Topics in Medicinal Chemistry ISBN: 9783662439135
Reducing Drug Attrition

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::e864fc299ac32e73298589e371735faf
https://doi.org/10.1007/978-3-662-43914-2

Lessons learned from candidate drug attrition

Autor: James R, Empfield, Paul D, Leeson

Publikováno v: IDrugs : the investigational drugs journal. 13(12)

Rising expenditure in pharmaceutical RD has not been matched by increased productivity. There is an urgent need to solve the current high levels of pipeline attrition. Changing the current failed model of drug discovery and development, in which high

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::24ef6299b112b361beafece8aada93a9
https://pubmed.ncbi.nlm.nih.gov/21154145