CAS 790299-79-5 Pharmaceutical Raw Materials Masitinib High Purity
Zhongshan Latterson Biotechnology Co., Ltd., is a comprehensive pharmaceutical enterprise, which specialized in bio-pharmaceutical technology over 7 years. The company is located in Zhongshan City, Guangdong Province , China.
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Product Details:

Description:

Masitinib aims to slow progression of ALS by reducing inflammation. A kinase inhibitor, masitinib blocks mast cell-mediated degranulation, the release of cytotoxic substances that might further damage the motor nerves. Marketed by AB Science under the name Kinavet, masitinib is currently being used to treat certain cancers in dogs. It is important to note that the company is also exploring the use of its kinase inhibitor in many other diseases, such as multiple sclerosis, Alzheimer’s and different types of cancer, among others.
Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicity. Phase II clinical trials demonstrate that Masitinib appears to be effective as a first-line treatment of advanced GIST with comparable results to imatinib in terms of safety and response. PFS and in particular OS data show promise that masitinib may provide sustainable benefits.
Masitinib, also known as methotrexate masitinib, is studied and developed by the AB Science, a platelet-derived growth factor alpha/beta receptor tyrosine kinase inhibitor for the treatment of multiple myeloma, gastrointestinal stromal tumors and prostate cancer. The drug had respectively, been entitled by FDA for the treatment of pancreatic cancer and ALS orphans disease in 2009 and 2015. On August 8, 2016, it has qualified as EMA orphan drug.

Application:

Masitinib is a novel kind of oral administrated tyrosine kinase inhibitors that could be targeted to immunizing important cellular mast cells and macrophages by inhibiting a certain amount of kinase. Based on its unique mechanism of action, masitinib can be developed for application in tumors, inflammatory diseases and certain central nervous system diseases. In the oncology, due to its immunotherapy effect, Masitinib may affect the survival period of cancer patients (single administration or in combination with chemotherapy). By acting on mast cells and microglia, and further inhibiting the activation of the inflammatory process, Masitinib is effective against certain inflammatory, central nervous system disorders as well as symptoms associated with degeneration of these diseases.

Masitinib, at a concentration of ≤ 500 nM, it is a kind of ATP competitive inhibitors. Masitinib can also effectively inhibit the recombinant PDGFR and intracellular kinase Lyn, and FGFR3. However, Masitinib has a weak inhibitory effect on ABL and c-Fms. Masitinib acts on de-granulation, cytokine production, and bone marrow mast cell migration with the inhibitory effect being much stronger than imatinib. In Ba/F3 cells expressing human wild-type KIT, Masitinib can inhibit the SCF (stem cell factor)-induced cell proliferation with an IC50 being 150 nM and an IC50 value of being larger than 10 μM when inhibiting the IL-3 stimulated proliferation. In Ba/F3 cells expressing PDGFR-α, Masitinib is capable of inhibiting the PDGF-BB stimulated proliferation and PDGFR-alpha tyrosine phosphorylation with an IC50 of 300 nM. Masitinib acts on mast cell tumor cell lines and BMMC, and also inhibits the stimulated phosphorylation of human KIT tyrosine. Masitinib takes effect on the Ba/F3 cells to suppress the KIT-acquired functional mutations which include V559D mutations and Δ27 mutations with IC50s of 3 and 5 nM, respectively. Masitinib inhibits the cell proliferation of mast cell tumor cell lines including HMC-1α155 and FMA3 cells with the IC50 of 10 and 30 nM, respectively. Masitinib acts on two new ISS cell lines, inhibits cell growth and phosphorylation of PDGFR, indicating that Masitinib inhibits primary and metastatic ISS cell lines and is helpful in the clinical management of ISS. 30 mg/kg Masitinib, when acting on the Ba/F3 transplanted tumor model expressing Δ27, is capable of inhibiting tumor growth and improving the survival time of the culture medium, and is non-toxic to both the heart and the gene. Daily oral administration of 12.5 mg/kg Masitinib improves all TTP (the grown tumor with the time). When the Masitinib and gemcitabine are used in combination to fight against the proliferation of the anti-gemcitabine cell lines during Mia Paca2 and Panc1 proliferation, they exhibit synergetic effects.

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