Chemistry:Masitinib
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] In addition to cKit, Masitinib also has additional targets, and it inhibits 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]
Society and culture
Legal status
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][11] European approval of masitinib for treatment of amyotrophic lateral sclerosis (Alsitek) was also refused in 2018.[12][13]
In June 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended the refusal of a marketing authorization for Masitinib AB Science, a medicine intended for the treatment of amyotrophic lateral sclerosis, a rare disease of the nervous system leading to loss of muscle function and paralysis.[14][15] In October 2024, following a re-examination, the CHMP confirmed its recommendation to refuse the granting of a conditional marketing authorization for Masitinib AB Science.[16]
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. 17 September 2018. 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). 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). July 2016. doi:10.1186/s12974-016-0620-9. PMID 27400786.
- ↑ "Masipro EPAR". 18 May 2017. https://www.ema.europa.eu/en/medicines/human/EPAR/masipro.
- ↑ 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 EPAR". 18 April 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/alsitek.
- ↑ "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.
- ↑ "Masitinib AB Science EPAR". 27 June 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/masitinib-ab-science. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ↑ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 June 2024". 28 June 2024. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-24-27-june-2024.
- ↑ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 14-17 October 2024". 18 October 2024. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-14-17-october-2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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