Masitinib (AB1010)

Alias: AB-1010; AB 1010; AB1010; Masitinib; Brand name: Kinavet; Masivet.
Cat No.:V0576 Purity: ≥98%
Masitinib (formerly also known as AB1010) is a novel, potent, orally bioavailable, selective and multi-targeted 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 (AB1010) Chemical Structure CAS No.: 790299-79-5
Product category: PDGFR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
50mg
100mg
250mg
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Other Forms of Masitinib (AB1010):

  • Masitinib Mesylate
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Masitinib (formerly also known as AB1010) is a novel, potent, orally bioavailable, selective and multi-targeted 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 PDGFR, FGFR3, c-Kit (the stem cell factor receptor), and, to a lesser extent, FAK. It also selectively binds to and mutates the stem cell factor receptor (SCFR). Consequently, in cancer cell types that overexpress these RTKs, tumor cell proliferation may be inhibited.

Biological Activity I Assay Protocols (From Reference)
Targets
Kit (IC50 = 200 nM); Lyn B (IC50 = 510 nM); PDGFRα (IC50 = 540 nM); PDGFRβ (IC50 = 800 nM); Abl1 (IC50 = 1.20 μM)
ln Vitro

Masitinib exhibits competitive inhibitory effects against ATP at concentrations ≤500 nM. Additionally, recombinant PDGFR, intracellular kinase Lyn, and fibroblast growth factor receptor 3 are all potently inhibited by misatkinib. Masitinib, on the other hand, shows only modest inhibition of c-Fms and Abl. Compared to imatinib, mastitinib more potently inhibits bone marrow mast cell migration, cytokine production, and degranulation. Masitinib inhibits SCF (stem cell factor)-induced cell proliferation in Ba/F3 cells expressing human wild-type Kit with an IC50 of 150 nM, whereas the IC50 for inhibiting IL-3-stimulated proliferation is at roughly >10 μM. Masitinib inhibits PDGFRα tyrosine phosphorylation and PDGF-BB-stimulated proliferation in Ba/F3 cells expressing PDGFRα, with an IC50 of 300 nM. In BMMC and mastocytoma cell lines, mitinib also inhibits the SCF-stimulated tyrosine phosphorylation of human Kit. Masitinib suppresses Kit gain-of-function mutants, such as the Δ27 mouse mutant and the V559D mutant, which have IC50 values of 3 and 5 nM in Ba/F3 cells. Masitinib has an IC50 of 10 nM for HMC-1α155 and 30 nM for FMA3, two mastocytoma cell lines whose cell proliferation is inhibited[1]. Two new ISS cell lines show that Masitinib inhibits PDGFR phosphorylation and cell growth, indicating that it is active against both primary and metastatic ISS cell lines and may help with ISS clinical management[2].

ln Vivo
Masitinib prevents tumor growth and lengthens the median survival time in Ba/F3 tumor models that express Δ27 at 30 mg/kg, all without causing genotoxicity or cardiotoxicity[1].
Masitinib (12.5 mg/kg/d, p.o.) improves overall TTP (time-to-tumor progression) when compared to a placebo in dogs[3].
Enzyme Assay
A 96-well microtitre plate is coated with 0.25 mg/mL poly(Glu, Tyr 4:1) for an entire night. It is then rinsed twice with 250 µL of washing buffer (10 mM phosphate-buffered saline [pH 7.4] and 0.05% Tween 20) and allowed to dry at room temperature for two hours. The assays are conducted at room temperature in a final volume of 50 µL of kinase buffer (10 mM MgCl2, 1 mM MnCl2, 1 mM sodium orthovanadate, 20 mM HEPES, pH 7.8) that contains recombinant enzyme and ATP at a concentration of at least twice the Km for each enzyme to guarantee a linear reaction rate. The enzyme is added to start the reaction, and it is stopped by adding one reaction volume (50 μL) of 100 mM EDTA per 5mol/Lurea mix. Plates are triple-washed and then incubated with tetramethylbenzidine and a 1:30,000 horseradish peroxidase-conjugated anti-phosphotyrosine monoclonal antibody. Spectrophotometry is used to measure the final reaction product at 450 nm.
Cell Assay
Microtitre plates are seeded with 104 cells/well in 100 μL of RPMI 1640 medium containing 10% foetal bovine serum at 37°C in order to conduct the Ba/F3 cell proliferation assay. 250 ng/mL of murine SCF or 0.1% of conditioned medium from X63-IL-3 cells are added to these, or not. Purified from the conditioned medium of SCF-producing CHO cells is the murine SCF that activates Kit. Masitinib-grown cells are incubated for 48 hours at 37°C with WST-1 reagent (10 μL/well) for three hours. Using a scanning multiwell spectrophotometer, the absorbance at 450 nm of the formazan dye indicates how much of it has formed. The spectrophotometer's background control is a blank well devoid of cells.
Animal Protocol
At 7 weeks old, male Nog-SCID mice are housed in a pathogen-free environment with filtered water and food available at all times. They experience a 12-hour light/12-hour dark cycle. According to the above description, Mia Paca-2 cells are cultured. Mice are given an injection into the right flank at day 0 (D0) containing 107 Mia Paca-2 cells in 200 µL PBS. After a tumor reaches the target size of approximately 200 mm3, it is allowed to grow for 1.5 to 4 weeks. In order to ensure that the mean body weight and tumor volume of each treatment group are well matched, animals are divided into four groups by day 28 (n = 7–8). The animals receive treatment for a maximum of four weeks, following which they are sacrificed. The treatments were as follows: a) daily gavage with 100 mg/kg masitinib; b) intraperitoneal (i.p.) injection of 50 mg/kg gemcitabine twice a week; c) daily gavage with 100 mg/kg masitinib; or d) a combination of daily gavage with 100 mg/kg masitinib and i.p. injection of 50 mg/kg gemcitabine twice a week. Callipers are used to measure the size of tumors, and the formula volume=(length × width2)/2 is used to estimate the tumor volume. (100) × (median tumor volume of treated group)/(median tumor volume of control group) is the formula for the tumor growth inhibition ratio.
References

[1]. Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT. PLoS One, 2009, 4(9), e7258.

[2]. 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]. Masitinib is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med, 2008, 22(6), 1301-1309.

[4]. Masitinib (AB1010), from canine tumor model to human clinical development: where we are? Crit Rev Oncol Hematol. 2014 Jul;91(1):98-111.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C28H30N6OS
Molecular Weight
498.64
Exact Mass
498.22
Elemental Analysis
C, 67.44; H, 6.06; N, 16.85; O, 3.21; S, 6.43
CAS #
790299-79-5
Appearance
Off-white to pale yellow solid powder
SMILES
CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC(=CS4)C5=CN=CC=C5
InChi Key
WJEOLQLKVOPQFV-UHFFFAOYSA-N
InChi Code
InChI=1S/C28H30N6OS/c1-20-5-10-24(16-25(20)31-28-32-26(19-36-28)23-4-3-11-29-17-23)30-27(35)22-8-6-21(7-9-22)18-34-14-12-33(2)13-15-34/h3-11,16-17,19H,12-15,18H2,1-2H3,(H,30,35)(H,31,32)
Chemical Name
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide
Synonyms
AB-1010; AB 1010; AB1010; Masitinib; Brand name: Kinavet; Masivet.
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~100 mg/mL (~200.5 mM)
Water: <1 mg/mL
Ethanol: ~4 mg/mL (~8.0 mM)
Solubility (In Vivo)
4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.0055 mL 10.0273 mL 20.0545 mL
5 mM 0.4011 mL 2.0055 mL 4.0109 mL
10 mM 0.2005 mL 1.0027 mL 2.0055 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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.
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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05441488 Recruiting Drug: Placebo
Drug: Masitinib (4.5)
Progressive Multiple Sclerosis AB Science June 28, 2022 Phase 3
NCT05047783 Recruiting Drug: Masitinib Mesylate
Drug: Placebo
Covid19
SARS-CoV2 Infection
AB Science November 23, 2021 Phase 2
NCT05564169 Not yet recruiting Drug: Placebo
Drug: Masitinib (4.5)
Alzheimer Disease AB Science January 2024 Phase 3
NCT04333108 Recruiting Drug: Masitinib
Other: Placebo
Indolent Systemic Mastocytosis AB Science July 1, 2020 Phase 3
NCT04622865 Recruiting Drug: Masitinib
Drug: Isoquercetin
SARS-CoV 2
COVID-19
AB Science June 1, 2020 Phase 2
Biological Data
  • Masitinib (AB1010)

    Masitinib inhibition of KIT in intact cells. PLoS One. 2009; 4(9): e7258.

  • Masitinib (AB1010)

    Masitinib inhibits tumour growth in vivo. PLoS One. 2009; 4(9): e7258.


  • Masitinib (AB1010)

    Effect of masitinib on BCR-ABL and PDGFRα.

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