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10mg |
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50mg |
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100mg |
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Masitinib Mesylate, the mesylate salt of Masitinib (AB-1010; AB1010) is an orally bioavailable, selective and multi-targeted tyrosine kinase inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, it shows weak inhibition to ABL and c-Fms. Masitinib selectively binds to and inhibits both the wild-type and mutated forms of the stem cell factor receptor (c-Kit; SCFR); PDGFR; FGFR3; and, to a lesser extent, FAK. As a consequence, tumor cell proliferation may be inhibited in cancer cell types that overexpress these RTKs.
ln Vitro |
At doses ≤500 nM, masatinib inhibits ATP competitively. Additionally, mashitinib strongly inhibits the intracellular kinase Lyn, recombinant PDGFR, and, to a lesser degree, fibroblast growth factor receptor 3. Masitinib, on the other hand, only slightly inhibited c-Fms and Abl. Compared to imatinib, mastitinib more potently suppresses bone marrow mast cell migration, cytokine generation, and degranulation. Masitinib has an IC50 of 150 nM for inhibiting SCF (stem cell factor)-induced cell proliferation in Ba/F3 cells expressing human wild-type Kit, whereas the IC50 is roughly >10 μM for inhibiting IL-3-stimulated proliferation. Masitinib, with an IC50 of 300 nM, suppresses PDGFRα tyrosine phosphorylation and PDGF-BB-stimulated proliferation in Ba/F3 cells that express PDGFRα. Additionally, in BMMC and mastocytoma cell lines, misitinib prevents SCF-stimulated tyrosine phosphorylation of human Kit. With IC50s of 3 and 5 nM, respectively, masatidinib inhibits Kit gain-of-function mutants in Ba/F3 cells, such as the Δ27 murine mutant and the V559D mutant. With IC50s of 10 and 30 nM, respectively, mastitinib inhibits cell growth in mastocytoma cell lines, such as HMC-1α155 and FMA3 [1]. Two new ISS cell lines showed growth and PDGFR phosphorylation, indicating that Masitinib exhibits efficacy against primary and metastatic ISS cell lines and could help with ISS clinical care [2].
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ln Vivo |
In a Ba/F3 tumor model expressing Δ27, methitinib mesylate (30 mg/kg) reduces tumor growth and lengthens the median survival time without causing genotoxicity or cardiotoxicity [1]. When compared to a placebo, methitinib mesylate (12.5 mg/kg/d, po) lengthens the period before tumor growth [3].
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Animal Protocol |
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References |
[1]. Dubreuil P, et al. Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT. PLoS One, 2009, 4(9), e7258.
[2]. Lawrence J, et al. Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells. Vet Comp Oncol, 2011, doi: 10.1111/j.1476-5829.2011.00291.x. [3]. Hahn KA, et al. Masitinib is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med, 2008, 22(6), 1301-1309. [4]. Marech I, et al. Masitinib (AB1010), from canine tumor model to human clinical development: where we are? Crit Rev Oncol Hematol. 2014 Jul;91(1):98-111 |
Molecular Formula |
C29H34N6O4S2
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Molecular Weight |
594.74
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CAS # |
1048007-93-7
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Related CAS # |
Masitinib;790299-79-5
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
S1C([H])=C(C2=C([H])N=C([H])C([H])=C2[H])N=C1N([H])C1=C(C([H])([H])[H])C([H])=C([H])C(=C1[H])N([H])C(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])=O.S(C([H])([H])[H])(=O)(=O)O[H]
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Synonyms |
Masitinib mesilate Masitinib Mesylate Salt Masitinib Mesylate
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
1M HCl : 100 mg/mL (~168.14 mM)
DMSO : ≥ 30 mg/mL (~50.44 mM) |
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.6814 mL | 8.4070 mL | 16.8141 mL | |
5 mM | 0.3363 mL | 1.6814 mL | 3.3628 mL | |
10 mM | 0.1681 mL | 0.8407 mL | 1.6814 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT05047783 | Recruiting | Drug: Masitinib Mesylate Drug: Placebo |
Covid19 SARS-CoV2 Infection |
AB Science | November 23, 2021 | Phase 2 |
NCT05441488 | Recruiting | Drug: Placebo Drug: Masitinib (4.5) |
Progressive Multiple Sclerosis | AB Science | June 28, 2022 | Phase 3 |
NCT05564169 | Not yet recruiting | Drug: Placebo Drug: Masitinib (4.5) |
Alzheimer Disease | AB Science | January 2024 | Phase 3 |
NCT05449444 | Recruiting | Drug: Masitinib 4.5 mg/kg/day | Mast Cell Activation Syndrome | AB Science | July 1, 2022 | Phase 2 |
NCT04622865 | Recruiting | Drug: Masitinib Drug: Isoquercetin |
SARS-CoV COVID-19 |
AB Science | June 1, 2020 | Phase 2 |
[1].Masitinib inhibition of KIT in intact cells. (A) Effect of masitinib and imatinib on SCF and IL-3-stimulated cell proliferation. Ba/F3 cells expressing wild-type (WT) human (hKIT) were incubated for 48 hours with 0.1% conditioned medium from X63-IL-3 cells (IL-3) (filled symbols) or 250 ng/ml murine SCF in the presence of various concentrations of masitinib and imatinib. Cell proliferation was assessed by WST-1 colorimetric assay. (B) Induction of apoptosis by masitinib in Ba/F3 cells expressing wild-type human KIT. Cells were incubated for 24 hours with stem cell factor (SCF) or 0.1% conditioned medium from X63-IL-3 cells (IL-3) in the presence of various concentrations of masitinib. Apoptosis was assessed via Annexin V-phycoerythrin (PE) and 7-amino-actinomycin D (7-AAD) staining, followed by fluorescence-activated cell sorting. A second dataset was acquired for an incubation of 48 hours to verify completeness of the apoptosis process. (C) Effect of masitinib and imatinib on KIT tyrosine phosphorylation in Ba/F3 cells (upper panels) and phosphorylation of the downstream targets AKT and ERK (lower panels). Ba/F3 cells expressing wild-type human KIT (hKIT WT) were incubated for 5 minutes with (+) or without (-) 250 ng/ml murine SCF in the presence of various concentrations of masitinib and imatinib. Tyrosine phosphorylation of KIT, AKT and ERK, were assessed by immunoprecipitation (IP) with the relevant antibody, followed by western blotting (Blot) with anti-phosphotyrosine (pTyr) or anti-KIT molecular weight. Results are representative of at least three independent experiments. MW = molecular weight markers. (D) Comparison of masitinib's and imatinib's ability to inhibit the FcεRI-mediated degranulation and cytokine production in cord blood derived mast cells (CBMC). Left: effect on the release of β-hexosaminidase by IgE-anti IgE activated CBMC after 30 minutes of stimulation. Right: effect on cytokine production by IgE-anti IgE-activated CBMC after 4 hours of simulation via ELISA assessment of TNF-α release. (E) The effect of masitinib and imatinib on the migration of murine BMMCs in response to rmSCF stimulation. td> |
Effect of masitinib on human and mouse KIT mutants. Effect of masitinib on the proliferation of Ba/F3 cells expressing wild-type (WT) or mutant human (hKIT) (Fig. 3A) or murine (Fig. 3C) KIT (mKIT). Assessment of proliferation was as described for Fig. 2A. Effect of masitinib on tyrosine phosphorylation of KIT mutants in Ba/F3 cells expressing the human V559D mutant (hKIT V559D) (Fig. 3B) or murine Δ27 mutant (mKIT Δ27) (Fig. 3D). KIT tyrosine phosphorylation was assessed as described in Fig. 2B. IP = immunoprecipitation; Blot = western blot; MW = molecular weight markers. td> |
Effect of masitinib on cell proliferation and KIT tyrosine phosphorylation in mastocytoma cell-lines and BMMC. (A) Effect of masitinib on the proliferation of human (HMC1, HMC-1α155) (filled symbols) and murine (P815, FMA3) mastocytoma cell lines harboring KIT mutants. Cells were incubated for 2 days with the indicated concentrations of masitinib. (B) western blotting analysis of HMC-1α155 tyrosine phosphorylation. (C) Effect of masitinib in the proliferation of BMMCs. BMMCs were incubated for 2 days with 250 ng/ml of stem cell factor (SCF) or 0.1% conditioned medium from X63-IL-3 cells (IL-3) with the indicated concentrations of masitinib. (D) Western blotting analysis of BMMC tyrosine phosphorylation. Cell proliferation was assessed by WST-1 colorimetric assay. Tyrosine phosphorylation of the KIT protein from sensitive cell types in (A) and (C) was analysed by immunoprecipitation (IP) and examined by western blotting (Blot) with antibodies to phosphotyrosine (anti-pTyr) or KIT (anti-Kit). MW = molecular weight. td> |