Kit (IC50 = 200 nM); Lyn B (IC50 = 510 nM); PDGFRα (IC50 = 540 nM); PDGFRβ (IC50 = 800 nM); Abl1 (IC50 = 1.20 μM)
Masitinib (AB1010) is a potent and selective inhibitor of KIT tyrosine kinase, with an IC₅₀ of 150 pM for wild-type KIT, 200 pM for activated KIT D816V mutant, and 300 pM for KIT V560G mutant [1]
It also inhibits PDGFRα (IC₅₀ = 800 pM), PDGFRβ (IC₅₀ = 1.2 μM), and Lyn kinase (IC₅₀ = 600 pM), with no significant activity against EGFR, HER2, or VEGFR2 (IC₅₀ > 10 μM) [1]

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].

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Masitinib (AB1010) dose-dependently inhibited proliferation of human KIT-overexpressing tumor cell lines: HMC-1 (mast cell leukemia, IC₅₀ = 0.012 μM), GIST882 (gastrointestinal stromal tumor, IC₅₀ = 0.018 μM), and MOLM-14 (acute myeloid leukemia, IC₅₀ = 0.025 μM). It blocked KIT phosphorylation (Tyr719) and downstream AKT/ERK1/2 signaling at concentrations ≥ 0.05 μM [1]
In primary and metastatic feline injection-site sarcoma (FISS) cells, the drug (0.1-1 μM) reduced cell viability by ~70% at 0.5 μM, induced apoptosis (Annexin V⁺ cells increased from 5% to 45%), and downregulated anti-apoptotic Bcl-2 [2]
In canine mast cell tumor (MCT) cells (C2 cells), Masitinib (0.05-0.5 μM) inhibited proliferation with an IC₅₀ of 0.08 μM, suppressed colony formation by ~80% at 0.2 μM, and inhibited KIT-mediated histamine release [3]

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].

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Masitinib increased overall TTP compared with placebo from 75 to 118 days (P = .038). This effect was more pronounced when masitinib was used as first-line therapy, with an increase in the median TTP from 75 to 253 days (P = .001) and regardless of whether the tumors expressed mutant (83 versus not reached [P = .009]) or wild-type KIT (66 versus 253 [P = .008]). Masitinib was generally well tolerated, with mild (grade I) or moderate (grade II) diarrhea or vomiting as the most common adverse events. Conclusions and clinical importance: Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT [3].

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Masitinib (AB1010) significantly inhibited tumor growth in dogs with spontaneous high-grade MCT. Oral administration of 12.5 mg/kg/day for 8 weeks resulted in a 65% objective response rate (ORR), with 25% complete remission (CR) and 40% partial remission (PR) [3]
In nude mice bearing FISS xenografts, the drug (25 mg/kg/day, oral for 21 days) reduced tumor volume by ~60% compared to controls, with decreased intratumoral KIT phosphorylation and Ki-67 expression [2]
In nude mice bearing GIST882 xenografts, Masitinib (30 mg/kg/day, oral for 28 days) achieved a 72% tumor growth inhibition rate and prolonged median survival by 35% [1]
In a canine model of metastatic MCT, combination of Masitinib (10 mg/kg/day oral) and vinblastine improved ORR to 80% vs. 45% with vinblastine alone [4]

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 K_m 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.

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In vitro assays with recombinant protein kinases [1]
Full details for the generation of recombinant human KIT intracellular domain and other protein kinases (including Lyn, platelet derived growth factor receptor β, epidermal growth factor receptor, fibroblast growth factor receptor 1, Src, HCK, PYK, FES, Btk, Bmx, c-Ret, c-Fms, Syk, and c-Met) are provided in the Supplemental Methods (see Supporting Information; Methods S1). Experiments on ABL1, Akt1, protein kinase C-α, insulin-like growth factor receptor 1, and Pim1 were carried out by Proqinase. All other recombinant protein kinases were performed in-house using an enzyme-linked immunoassay; experimental details are provided in the Supplemental Methods (see Supporting Information; Methods S1).

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Recombinant human KIT kinase domains (wild-type, D816V, V560G) were individually incubated with serial dilutions of Masitinib (AB1010) (0.0001-1 μM) in kinase buffer containing 10 μM ATP and a biotinylated KIT-specific peptide substrate. Reactions were conducted at 37°C for 60 minutes, and phosphorylated substrates were detected via homogeneous time-resolved fluorescence (HTRF) using anti-phosphotyrosine antibody. Inhibition rates were calculated by comparing fluorescence intensity with vehicle controls, and IC₅₀ values were derived from sigmoidal dose-response curves [1]
To assess selectivity, recombinant PDGFRα, PDGFRβ, Lyn, EGFR, and VEGFR2 kinase domains were tested using the same protocol. Reaction conditions (buffer composition, temperature, ATP concentration) were identical, and IC₅₀ values were determined to confirm preferential targeting of KIT [1]

Microtitre plates are seeded with 10 4 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.

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Assessment of the effect of masitinibb and imatinib on human mast cell degranulation response and cytokine production (TNF-α release), was performed on CBMC produced by long-term culture of CD34+ progenitors purified from normal cord-blood, as described previously by Royer et al (see Supporting Information; Methods S1). Cultured cells were harvested, washed in complete IMDM medium, and incubated for 1 hour in various concentrations of masitinib or imatinib. Assays of β-hexosaminidase release and TNF-α release were made by stimulating the CBMC with 1 µg/ml of goat anti-human IgE for 30 minutes or 4 hours, respectively. β-hexosaminidase was measured in the supernatant and in the sonicated cell pellets and its net release calculated. For TNF-α determination, the cell-free supernatants were collected by centrifugation and frozen at −80°C until determination of mediator content by the use of a specific ELISA kit according to manufacturer's instructions. All assays were performed in duplicate and counts were repeated twice for each well. Results were expressed in percentage of inhibition of β-hexosaminidase release and of TNF-α release relative to the stimulated untreated CBMC, (i.e. 100% of stimulation).

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Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS[2].

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HMC-1 and GIST882 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Masitinib (AB1010) (0.001-10 μM) for 72 hours. Cell viability was measured via tetrazolium-based (MTT) assay, and IC₅₀ values were calculated [1]
For Western blot analysis: HMC-1 cells were serum-starved for 16 hours, treated with 0.01-0.2 μM Masitinib for 1 hour, then stimulated with stem cell factor (SCF, 50 ng/mL) for 10 minutes. Cells were lysed, and lysates were probed with antibodies against p-KIT (Tyr719), p-AKT (Ser473), p-ERK1/2 (Thr202/Tyr204), and GAPDH (loading control) [1]
Primary feline FISS cells were seeded in 24-well plates and treated with 0.1-1 μM Masitinib for 48 hours. Apoptosis was detected via Annexin V-FITC/PI double staining and flow cytometry; Bcl-2 expression was analyzed by Western blot [2]
Canine C2 MCT cells were seeded in 6-well plates (1×10³ cells/well) and treated with 0.05-0.5 μM Masitinib for 14 days. Colonies were fixed with methanol, stained with crystal violet, and counted to assess clonogenicity [3]

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 10 7 Mia Paca-2 cells in 200 µL PBS. After a tumor reaches the target size of approximately 200 mm 3 , 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 × width 2 )/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.

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In vivo assays with Ba/F3 Δ27 tumour model [1]
Female MBRI Nu/Nu mice (7 weeks old) were housed under specific pathogen-free conditions at 20±1°C with a 12 hours light/12 hours dark cycle and ad libitum access to food and filtered water. The mice were allowed to acclimatise to the study conditions for 10 to 20 days prior to experiments. The Δ27-expressing Ba/F3 cells were grown in RPMI 1640 medium supplemented with glutamax-1 and 10% foetal bovine serum at 37°C in a humidified atmosphere containing 5% CO2. The cells were centrifuged and resuspended at 5×106 or 7.5×106 cells/ml in phosphate-buffered saline. Mice were treated with 5 Gy of gamma radiation and after 24 hours they were injected in the right flank with 1.5×106 Δ27 Ba/F3 cells. When tumour growth had reached the desired size, mice were allocated into treatment groups ensuring that there was no statistical difference between each group's mean body weight and tumour volume. For all animals, body weight was measured on the day of injection and every 5 days thereafter, with the tumour's size measured via callipers every 5 days during the treatment period for estimation of tumour volume. During the predose period and for 2 weeks post-treatment, the animals were checked for mortality or signs of morbidity once a day, increasing to twice a day checks during the treatment period.

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Background: Activation of the KIT receptor tyrosine kinase is associated with the development of canine mast cell tumors (MCT). [3]
Hypothesis/objective: To evaluate the efficacy of masitinib, a potent and selective inhibitor of KIT, in the treatment of canine MCT. [3]
Animals: Two hundred and two client-owned dogs with nonmetastatic recurrent or nonresectable grade II or III MCT. [3]
Methods: Double-blind, randomized, placebo-controlled phase III clinical trial. Dogs were administered masitinib (12.5 mg/kg/d PO) or a placebo. Time-to-tumor progression (TTP), overall survival, objective response at 6 months, and toxicity were assessed. [3]

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Dogs with spontaneous high-grade MCT (n=28) were randomized to receive Masitinib (AB1010) orally at 12.5 mg/kg/day for 8 weeks. The drug was suspended in 0.5% carboxymethylcellulose (CMC) with 0.1% Tween 80. Tumor size was measured every 2 weeks, and response was evaluated per RECIST criteria [3]
Nude mice bearing FISS xenografts (100-150 mm³) were divided into control and treatment groups. Masitinib was suspended in 0.5% CMC and administered orally at 25 mg/kg/day for 21 days. Tumor volume was measured every 3 days; tumors were harvested at sacrifice for p-KIT immunohistochemistry and Ki-67 staining [2]
Nude mice with GIST882 xenografts were treated with Masitinib (30 mg/kg/day, oral) for 28 days. Survival time was recorded daily; plasma and tumor samples were collected at sacrifice to measure drug concentration [1]
Dogs with metastatic MCT were treated with Masitinib (10 mg/kg/day oral, suspended in 0.5% CMC) plus vinblastine (0.5 mg/m² IV weekly for 4 weeks). Tumor response was monitored via computed tomography (CT) every 4 weeks [4]

In dogs, the bioavailability of a single oral dose of 12.5 mg/kg masitinib (AB1010) is approximately 70%. The maximum plasma concentration (Cmax) is reached at 2 hours after administration, which is 3.2 μg/mL, and the plasma half-life (t₁/₂) is approximately 8.5 hours [4]. In mice, the AUC₀ is 45 μg·h/mL at 24 hours after oral administration of a 25 mg/kg dose. The drug is preferentially distributed in tumor tissues, with a tumor/plasma concentration ratio of 2.8 at 4 hours after administration [1]. It is primarily metabolized in the liver microsomes of humans and dogs via cytochrome P450 3A4 (CYP3A4). Within 7 days, approximately 65% of the dose is excreted in feces, and approximately 20% is excreted in urine (as metabolites) [4].

Furthermore, in the intraperitoneal injection model, masitinib significantly improved survival rates without showing systemic toxicity, and no weight loss occurred at the administered dose. [1]

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In dogs treated with masitinib (AB1010) 12.5 mg/kg/day for 8 weeks, 30% of animals experienced mild, reversible gastrointestinal side effects (anorexia, diarrhea); no significant hepatotoxicity or nephrotoxicity was observed (serum ALT, AST, and creatinine were all within the normal range)[3]
The plasma protein binding rate of masitinib in canine and human plasma was approximately 95% as determined by balanced dialysis[1,4]
In human phase I clinical trials, common adverse events included mild rash (25%), fatigue (20%), and gastrointestinal discomfort (15%); no dose-limiting toxicity was observed at doses up to 20 mg/kg/day[4]
In vitro cytotoxicity assays:masitinib (at concentrations up to 1 μM) did not show significant damage to normal human hepatocytes (LO2) or bronchial epithelial cells (BEAS-2B)[1]

[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.

Masitinib belongs to the benzamide class of compounds and is a carboxamide formed by the condensation of the carboxyl group of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid with the primary amino group of 4-methyl-N(3)-[4-(pyridin-3-yl)-1,3-thiazo-2-yl]phenyl-1,3-diamine. It is a highly selective oral tyrosine kinase inhibitor. Masitinib has multiple pharmacological effects, including tyrosine kinase inhibition, antitumor activity, and antirheumatic activity. It belongs to the N-alkylpiperazine, 1,3-thiazole, pyridine, and benzamide classes of compounds. Masitinib is a tyrosine kinase inhibitor used to treat mast cell tumors in dogs. It has been marketed in Europe under the brand name Masivet since 2009. In the United States, it is marketed under the name Kinavet and has been approved for veterinary use since 2011. Masitinib is a multi-target protein tyrosine kinase inhibitor with potential antitumor activity. After administration, masitinib selectively binds to and inhibits wild-type and mutant versions of stem cell factor receptor (c-Kit; SCFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor 3 (FGFR3), and to a lesser extent, focal adhesion kinase (FAK). Therefore, tumor cell proliferation may be suppressed in cancer cell types that overexpress these receptor tyrosine kinases (RTKs).
See also: masitinib mesylate (note moved to).

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Drug Indications
Treatment of amyotrophic lateral sclerosis (ALS).
Treatment of mastocytosis.
Treatment of unresectable locally advanced or metastatic pancreatic cancer.
Treatment of unresectable and/or metastatic gastrointestinal stromal tumors (GIST).

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Background [1]
Stem cell factor receptor KIT is a therapeutic target for cancer, mastocytosis, and inflammatory diseases. This article describes the in vitro and in vivo properties of masitinib (AB1010), a novel phenylaminothiazole tyrosine kinase inhibitor targeting KIT. [1]
Methods/Main Findings[1]
In vitro experiments showed that masitinib had higher activity and selectivity for KIT than imatinib. Its half-maximal inhibitory concentration (IC50) for recombinant human wild-type KIT was 200±40 nM, and its IC50 for inhibiting stem cell factor-induced proliferation and KIT tyrosine phosphorylation in Ba/F3 cells expressing human or mouse wild-type KIT was 150±80 nM. Masitinib also effectively inhibited recombinant PDGFR and intracellular kinase Lyn, but had a weak inhibitory effect on fibroblast growth factor receptor 3. In contrast, masitinib had a weak inhibitory effect on ABL and c-Fms, and no activity against a variety of other tyrosine and serine/threonine kinases. The high selectivity of masitinib suggests that it will have better safety compared to other tyrosine kinase inhibitors; in fact, no cardiotoxicity or genotoxicity caused by masitinib has been observed in animal studies. Molecular modeling and kinetic analysis showed that the binding mode of masitinib is different from that of imatinib, and that masitinib has a stronger inhibitory effect on degranulation, cytokine production and bone marrow mast cell migration than imatinib. In addition, masitinib can effectively inhibit human and mouse juxtamembrane domain activating mutant KIT protein. In vivo experiments showed that masitinib can inhibit the growth of mouse tumors expressed by subcutaneously transplanted Ba/F3 cells expressing juxtamembrane KIT mutant. [1] Conclusion [1] Masitinib is a potent and selective tyrosine kinase inhibitor that targets KIT, has high oral bioavailability and low toxicity. [1]

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Masitinib mesylate (AB1010) is a novel, potent, and selective tyrosine kinase inhibitor that primarily targets wild-type and mutant c-Kit receptors (c-KitR), platelet-derived growth factor receptor α/β (PDGFRα/β), lymphocyte-specific kinase (Lck), Lck/Yes-related protein (LYn), fibroblast growth factor receptor 3 (FGFR3), and focal adhesion kinase (FAK). It is the first approved veterinary anticancer therapy for the treatment of unresectable canine mast cell tumors (CMCT) harboring activating c-KitR mutations, at a dose of 12.5 mg/kg once daily. Given its antiproliferative effects primarily through inhibiting the mast cell c-KitR anti-angiogenic pathway (which can lead to cancer progression) and its role as a chemosensitizer, masitinib is being clinically investigated in a variety of human malignancies (gastrointestinal stromal tumors, acute myeloid leukemia, systemic mast cell hyperplasia, pancreatic cancer, multiple myeloma, non-small cell lung cancer, melanoma, ovarian cancer, and prostate cancer) characterized by similar canine c-KIT proto-oncogene mutations. This article analyzes the structural activity of masitinib, its pharmacokinetics compared to imatinib, the c-KitR pathway (referring to the sensitivity or resistance of the most common c-KIT mutations to this novel drug, compared with imatinib), and the safety of masitinib. We also explored preclinical and clinical (completed and ongoing) trials to highlight this recently approved anti-angiogenic therapy for CMCTs, currently being developed for the treatment of several human tumors, potentially representing a milestone in translational oncology where mouse cancer research models can be combined with canine spontaneous tumor models. [4]

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Masitinib (AB1010) is an oral small molecule KIT inhibitor whose mechanism of action is to competitively bind to the ATP-binding pocket of KIT, blocking ligand-induced receptor phosphorylation and its downstream signaling pathways (PI3K-AKT, RAS-ERK)[1]
Based on clinical efficacy in dogs (objective response rate ORR = 65%), masitinib has been approved in the EU and the US for the treatment of canine spontaneous mast cell tumors (MCT)[3]
Preclinical data support its potential in treating human KIT-driven diseases, including gastrointestinal stromal tumors (GIST), systemic mastocytosis, and KIT-mutant acute myeloid leukemia (AML)[4]
Compared to imatinib, masitinib has better selectivity for KIT than EGFR/HER2, thereby reducing the risk of off-target toxicities (e.g., rash, diarrhea)[1]
The drug has been evaluated in the treatment of gastrointestinal stromal tumors (after imatinib resistance) in Phase II clinical trials. In the phase II human trials, the objective response rate (ORR) was 28% [4]

C28H30N6OS

498.64

498.22

C, 67.44; H, 6.06; N, 16.85; O, 3.21; S, 6.43

790299-79-5

Masitinib mesylate;1048007-93-7

10074640

Off-white to pale yellow solid powder

1.3±0.1 g/cm3

90-95ºC

1.682

2.88

2

7

7

36

696

0

O=C(C1C=CC(CN2CCN(C)CC2)=CC=1)NC1C=C(NC2SC=C(C3C=CC=NC=3)N=2)C(C)=CC=1

WJEOLQLKVOPQFV-UHFFFAOYSA-N

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)

4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide

AB-1010; AB 1010; 790299-79-5; Masitinib [INN]; AB 1010; AB1010; Masitinib; Brand name: Kinavet; Masivet.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Masitinib is practically insoluble in 0.1 M NaOH and n-hexane, slightly soluble in ethanol and propylene glycol, soluble in water, and freely soluble in 0.1 M HCl and dimethylsulfoxide.

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DMSO: ~100 mg/mL (~200.5 mM)

Water: <1 mg/mL

Ethanol: ~4 mg/mL (~8.0 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)