Masitinib (AB1010)

Catalog No.S1064

Molecular Weight(MW): 498.64

Masitinib is a novel inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, weak inhibition to ABL and c-Fms. Phase 3.

3 Customer Reviews

H&E stained histology slides of A), C), and E) control implants and B), D), and F) drug-loaded implants for 14, 21 and 28 day time points respectively. Location of the implants is denoted by the asterisk ‘*’. Scale bar: 200 μm.

Biomaterials 2013 34, 9737-46. Masitinib (AB1010) purchased from Selleck.

Mol Cell Endocrinol, 2018, 470:75-83. Masitinib (AB1010) purchased from Selleck.
(E) Masitinib inhibits SCF-induced internalization of VE-cadherin. The HRMECs were pretreated with masitinib (1 lM) for 30 minutes before stimulation with rhSCF (50 ng/mL). The arrows in the left image indicate the disappearance of VE-cadherin at endothelial junctions that were positively stained for anti-ZO-1 IgGs (red). The arrows in the right image indicate VE-cadherin (green) internalization in endosomes that were positively stained for EEA1 (red). Internalization of endogenous VE-cadherin was quantified based on the percentage of HRMECs with intracellular acid-resistant vesicles (three independent experiments). Scale bar: 20 lm. All data are presented as mean 6 SEM (*P < 0.05 vs. PBS, #P < 0.05 vs. SCF only).

Invest Ophthalmol Vis Sci, 2016, 57(3):1201-6. Masitinib (AB1010) purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description

Masitinib is a novel inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, weak inhibition to ABL and c-Fms. Phase 3.

Features

Potential low side-effect profile.

Targets

Kit ^[1] (Cell-free assay)	Lyn B ^[1] (Cell-free assay)	PDGFRα ^[1] (Cell-free assay)	PDGFRβ ^[1] (Cell-free assay)	Abl1 ^[1] (Cell-free assay)	View More
200 nM	510 nM	540 nM	800 nM	1.20 μM	View More

In vitro

Masitinib is a competitive inhibitor against ATP at concentrations ≤500 nM. Masitinib also potently inhibits recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, Masitinib demonstrates weak inhibition of Abl and c-Fms. Masitinib more strongly inhibits degranulation, cytokine production, and bone marrow mast cell migration than imatinib. In Ba/F3 cells expressing human wild-type Kit, Masitinib inhibits SCF (stem cell factor)-induced cell proliferation with an IC50 of 150 nM, while the IC50 for inhibition of IL-3-stimulated proliferation is at approximately >10 µM. In Ba/F3 cells expressing PDGFRα, Masitinib inhibits PDGF-BB-stimulated proliferation and PDGFRα tyrosine phosphorylation with IC50 of 300 nM. Masitinib also causes inhibition of SCF-stimulated tyrosine phosphorylation of human Kit in mastocytoma cell-lines and BMMC. Masitinib inhibits Kit gain-of-function mutants, including V559D mutant and Δ27 mouse mutant with IC50 of 3 and 5 nM in Ba/F3 cells. Masitinib inhibits the cell proliferation of mastocytoma cell lines including HMC-1α155 and FMA3 with IC50 of 10 and 30 nM, respectively. ^[1] Masitinib inhibits cell growth and PDGFR phosphorylation in two novel ISS cell lines, which suggest that Masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS. ^[2]

In vivo

Masitinib inhibits tumour growth and increases the median survival time in Δ27-expressing Ba/F3 tumor models at 30 mg/kg, without cardiotoxicity or genotoxicity. ^[1] Masitinib (12.5 mg/kg/d PO) increases overall TTP (time-to-tumor progression) compared with placebo in dogs. ^[3] The combination of masitinib/gemcitabine shows synergy in vitro on proliferation of gemcitabine-refractory cell lines Mia Paca2 and Panc1, and to a lesser extent on Mia Paca-2 pancreatic tumours in Nog璖CID mice. ^[4]

Protocol

Kinase Assay:^[1]	+ Expand In vitro enzyme-linked immunoassay with recombinant protein kinases: A 96-well microtitre plateis coated overnight with 0.25 mg/ml poly(Glu,Tyr 4:1), rinsed twice with 250 µL of washing buffer (10 mM phosphate-buffered saline [pH 7.4] and 0.05% Tween 20) and dried for 2 hours at room temperature. Assays are performed at room temperature with a final volume of 50 µL in kinase buffer (10 mM MgCl₂, 1 mM MnCl₂, 1 mM sodium orthovanadate, 20 mM HEPES, pH 7.8) containing ATP at a concentration of at least twice the Km for each enzyme and an appropriate amount of recombinant enzyme to ensure a linear reaction rate. Reactions are initiated upon introduction of the enzyme and terminated with the addition of one reaction volume (50 μL) of 100 mM EDTA per 5 M urea mix. Plates are washed three times and incubated with 1:30,000 horseradish peroxidase-conjugated anti-phosphotyrosine monoclonal antibody, then washed three times and incubated with tetramethylbenzidine. The final reaction product is quantified by spectrophotometry at 450 nm.
Cell Research:^[1]	+ Expand Cell lines: Ba/F3 cells expressing wild-type or mutant human Kit, HMC1, HMC-1α155 Concentrations: 0.1 nM - 10 μM Incubation Time: 48 hours Method: For the assay of Ba/F3 cell proliferation, microtitre plates are seeded with a total of 10⁴ cells/well in 100 μL of RPMI 1640 medium with 10% foetal bovine serum at 37 °C. These are supplemented, or not, with either 0.1% conditioned medium from X63-IL-3 cells or 250 ng/mL murine SCF. The murine SCF, which activates Kit, is purified from the conditioned medium of SCF-producing CHO cells. Cells are grown for 48 hours at 37 °C with Masitinib and then incubated with 10 μL/well of WST-1 reagent for 3 hours at 37 °C. The amount of formazan dye formed is quantified by its absorbance at 450 nm using a scanning multiwell spectrophotometer. A blank well without cells is used as a background control for the spectrophotometer. (Only for Reference)
Animal Research:^[1]	+ Expand Animal Models: Ba/F3 Δ27 tumour model in female MBRI Nu/Nu mice Formulation: DMSO Dosages: 30 mg/kg (intraperitoneal) or 10, 30, or 45 mg/kg (orally). Administration: Intraperitoneal or orally administered. (Only for Reference)

References

[4] Humbert M, et al. PLoS One, 2010, 5(3), e9430.

+ Expand

Solubility (25°C)

In vitro	DMSO	100 mg/mL (200.54 mM)
	Ethanol	4 mg/mL (8.02 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 4% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing.	30mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Masitinib (AB1010) SDF

Molecular Weight	498.64
Formula	C₂₈H₃₀N₆OS
CAS No.	790299-79-5
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2018-10-19)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02490488	Unknown status	Ovarian Cancer	AB Science	April 2014	Phase 2
NCT02605044	Unknown status	2nd Line Metastatic Colorectal Cancer	AB Science	January 2014	Phase 3
NCT02009423	Unknown status	Gastro-Intestinal Stromal Tumour	AB Science	January 2014	Phase 3
NCT02588677	Completed	Amyotrophic Lateral Sclerosis (ALS)	AB Science	April 2013	Phase 2\|Phase 3
NCT01694277	Unknown status	Gastrointestinal Stromal Tumors	AB Science	April 2012	Phase 3
NCT01872598	Unknown status	Alzheimer Disease	AB Science	January 2012	Phase 3

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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c-Kit Signaling Pathway Map

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Axitinib : c-Kit, IC50=1.7 nM.
FDA-approved Kit Inhibitor

Imatinib Mesylate (STI571) : Approved by FDA for CML, GISTs and a number of other malignancies.
Newest Kit Inhibitor

Tyrphostin AG 1296 : An inhibitor of PDGFR with IC50 of 0.3-0.5 μM, inhibiting FGFR and c-Kit with IC50 of 12.3 μM and 1.8 μM in Swiss 3T3 cells.
Classic Kit Inhibitor

Dovitinib (TKI-258, CHIR-258) : Multitargeted RTK inhibitor for class III (FLT3/c-Kit), class IV (FGFR1/3) and class V (VEGFR1-4) RTKs.

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Masitinib (AB1010)