Chemistry:Masitinib
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| Trade names | Masivet, Kinavet |
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| Formula | C28H30N6OS |
| Molar mass | 498.65 g·mol−1 |
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Masitinib is a tyrosine-kinase inhibitor used in the treatment of mast cell tumours in animals, specifically dogs.[1][2] Since its introduction in November 2008 it has been distributed under the commercial name Masivet. It has been available in Europe since the second part of 2009. Masitinib has been studied for several human conditions including melanoma, multiple myeloma, gastrointestinal cancer, pancreatic cancer, Alzheimer disease, multiple sclerosis, rheumatoid arthritis, mastocytosis, amyotrophic lateral sclerosis and COVID-19.[3][4][5]
Mechanism of action
Masitinib is a tyrosine kinase inhibitor which inhibits tyrosine kinases, enzymes responsible for the activation of many proteins by signal transduction cascades. Specifically, masitinib targets the receptor tyrosine kinase c-Kit which is found to be overexpressed or mutated in several types of cancer.[2][6] Masitinib is also additional targets, it also inhibits the platelet derived growth factor receptor (PDGFR), lymphocyte-specific protein tyrosine kinase (Lck), focal adhesion kinase (FAK) and fibroblast growth factor receptor 3 (FGFR3) as well as CSF1R.[7][8]
Masitinib has been shown to block the replication of SARS-CoV-2 by inhibiting its main protease, 3CLpro. Masitinib showed >200-fold reduction in viral titers in the lungs and nose of mice infected with SARS-CoV-2.[3]
Clinical use
Masitinib was under investigation for the treatment of systemic mastocytosis (Masipro) but approval was denied in the EU in 2017 due to concerns "about the reliability of the study results" and major changes to the study design.[9][10]
European approval of masitinib for treatment of amyotrophic lateral sclerosis (Alsitek) was also refused in 2018.[11]
References
- ↑ "Masitinib is safe and effective for the treatment of canine mast cell tumors". Journal of Veterinary Internal Medicine 22 (6): 1301–1309. 2008. doi:10.1111/j.1939-1676.2008.0190.x. PMID 18823406.
- ↑ 2.0 2.1 Information about Masivet at the European pharmacy agency website
- ↑ 3.0 3.1 "Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2". Science 373 (6557): 931–936. August 2021. doi:10.1126/science.abg5827. PMID 34285133. Bibcode: 2021Sci...373..931D.
- ↑ "Orphan designation EU/3/16/1722 for masitinib mesilate for the treatment of amyotrophic lateral sclerosis.". European Medicines Agency. 2018-09-17. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2016/10/human_orphan_001821.jsp.
- ↑ "Masitinib for the treatment of mild to moderate Alzheimer's disease". Expert Review of Neurotherapeutics 15 (6): 587–596. June 2015. doi:10.1586/14737175.2015.1045419. PMID 25961655.
- ↑ "Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT". PLOS ONE 4 (9): e7258. September 2009. doi:10.1371/journal.pone.0007258. PMID 19789626. Bibcode: 2009PLoSO...4.7258D.
- ↑ "C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic". Veterinary Journal 205 (1): 5–10. July 2015. doi:10.1016/j.tvjl.2015.05.002. PMID 26021891.
- ↑ "Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis". Journal of Neuroinflammation 13 (1): 177. July 2016. doi:10.1186/s12974-016-0620-9. PMID 27400786.
- ↑ Refusal of the marketing authorisation for Masipro (masitinib). (PDF) EMA, 15 September 2017; retrieved 21 September 2017.
- ↑ "Masipro (masitinib)". Union Register of refused medicinal products for human use. Public Health - European Commission. https://ec.europa.eu/health/documents/community-register/html/ho26274.htm.
- ↑ "Alsitek (masitinib)". Union Register of refused medicinal products for human use. Public Health - European Commission. https://ec.europa.eu/health/documents/community-register/html/ho26580.htm.
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