Masitinib

SKU: orb1305268

Description

Masitinib (AB1010) is a tyrosine kinase inhibitor used in veterinary medicine to treat canine mast cell tumors, marketed as Masivet in Europe and Kinavet in the USA. Its research applications extend to investigating mast cell-related diseases and kinase signaling pathways in both in vitro and in vivo experimental models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 790299-79-5
• MW: 498.64
• Purity: 99.91%
• Formula: C₂₈H₃₀N₆OS
• SMILES: N(C1=NC(=CS1)C=2C=CC=NC2)C3=CC(NC(=O)C4=CC=C(CN5CCN(C)CC5)C=C4)=CC=C3C
• Target: Bcr-Abl,c-Kit,FAK,FGFR,PDGFR,Apoptosis,c-Fms,Hck,Src
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:250 mg/mL (501.36 mM);Ethanol:4 mg/mL (8.02 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.01 mM)

Bioactivity

• Target IC50:
  PDGFRβ:800 nM|PDGFRα:540 nM|LynB:510 nM|c-Kit:200 nM|Abl-1:1.20 μM
• In Vivo:
  Masitinib inhibits the proliferation of Ba/F3 cells expressing human wild-type KIT induced by stem cell factor, with an IC50 of 150 nM, and the proliferation induced by IL-3 with an IC50 value of >10 μM. In Ba/F3 cells expressing PDGFR-α, masitinib suppresses PDGF-BB-stimulated proliferation and PDGFR-α tyrosine phosphorylation, with an IC50 of 300 nM. At concentrations of ≤500 nM, masitinib acts as an ATP-competitive inhibitor. It also effectively inhibits recombinant PDGFR and the intracellular kinases Lyn and FGFR3. However, masitinib exhibits weak inhibition of ABL and c-Fms. In mammalian cell lines and BMMC, masitinib inhibits SCF-induced human Kit tyrosine phosphorylation. It inhibits KIT gain-of-function mutations in Ba/F3 cells, including the V559D and Δ27 mouse mutations, with IC50 values of 3 and 5 nM, respectively. In two novel ISS cell lines, masitinib inhibits cell growth and PDGFR phosphorylation, indicating its activity against primary and metastatic ISS cell lines and its potential utility in ISS clinical management. Masitinib provides stronger inhibition than imatinib on degranulation, cytokine production, and migration of bone marrow mast cells. It inhibits the proliferation of mastocytoma cell lines, including HMC-1α155 and FMA3, with IC50 values of 10 and 30 nM, respectively.
• In Vitro:
  Compared to a placebo, Masitinib (at a dosage of 12.5 mg/kg/d PO) significantly increased the overall TTP (tumor progression time) in dogs. In the Ba/F3 transplant tumor model expressing Δ27, Masitinib at 30 mg/kg inhibited tumor growth and extended the average survival time, without exhibiting cardiotoxicity or genotoxicity. Additionally, the combination of Masitinib and gemcitabine demonstrated a synergistic inhibitory effect on the proliferation of gemcitabine-resistant cell lines, Mia Paca2 and Panc1.
• Cell Research:
  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)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

c-Kit, cKit, CD117, AB-1010, AB1010, AB 1010, Abl1, Apoptosis, BcrAbl, cFms, c-Fms, Masitinib, Inhibitor, Hck, FAK, FGFR, Focal adhesion kinase, Fibroblast growth factor receptor, inhibit, Lyn B, Kit, PDGFRβ, PDGFRα, PDGFR, Platelet-derived growth factor receptor, PTK2, PTK2 protein tyrosine kinase 2, SCFR, Src

Compound Identifiers

PubChem CID

10074640