Synonyms: GS856553 | GW856553
Compound class:
Synthetic organic
Comment: Losmapimod is a p38 mitogen-activated kinase α/β inhibitor. It was originally developed by GlaxoSmithKline for cardiovascular disease, but this failed to show efficacy. Fulcrum acquired the drug and are repurposing it for the treatment of the progressive muscle wasting disorder facioscapulohumeral muscular dystrophy (FSHD) based on evidence that p38α regulates expression of the FSHD-related gene DUX4 [4-5].
![]() Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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References |
1. Aston NM, Bamborough P, Buckton JB, Edwards CD, Holmes DS, Jones KL, Patel VK, Smee PA, Somers DO, Vitulli G et al.. (2009)
p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression. J Med Chem, 52 (20): 6257-69. [PMID:19772287] |
2. O'Donoghue ML, Glaser R, Aylward PE, Cavender MA, Crisp A, Fox KA, Laws I, Lopez-Sendon JL, Steg PG, Theroux P et al.. (2015)
Rationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE trial. Am Heart J, 169 (5): 622-630.e6. [PMID:25965709] |
3. O'Donoghue ML, Glaser R, Cavender MA, Aylward PE, Bonaca MP, Budaj A, Davies RY, Dellborg M, Fox KA, Gutierrez JA et al.. (2016)
Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial. JAMA, 315 (15): 1591-9. [PMID:27043082] |
4. Oliva J, Galasinski S, Richey A, Campbell AE, Meyers MJ, Modi N, Zhong JW, Tawil R, Tapscott SJ, Sverdrup FM. (2019)
Clinically Advanced p38 Inhibitors Suppress DUX4 Expression in Cellular and Animal Models of Facioscapulohumeral Muscular Dystrophy. J Pharmacol Exp Ther, 370 (2): 219-230. [PMID:31189728] |
5. Rojas LA, Valentine E, Accorsi A, Maglio J, Shen N, Robertson A, Kazmirski S, Rahl P, Tawil R, Cadavid D et al.. (2020)
p38α Regulates Expression of DUX4 in a Model of Facioscapulohumeral Muscular Dystrophy. J Pharmacol Exp Ther, 374 (3): 489-498. [PMID:32576599] |