Masitinib (AB1010) (Synonyms: AB-1010, Masican, Masiviera)

Cell lines

Ba/F3 cells, HMC-1α155 and FMA3 cells, bone marrow cells

Preparation method

The solubility of this compound in DMSO is > 25 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

37°C

Applications

Masitinib inhibited human mast cell degranulation, cytokine production and migration of bone marrow cells. In Ba/F3 cells, masitinib dose-dependently inhibited cell proliferation induced by the V559D mutant, commonly associated with GIST (exon 11), with an IC50 of 3.0 ± 0.1 nM. Masitinib dose-dependently inhibited Δ27 KIT-dependent proliferation of Ba/F3 cells with an IC50 of 5.0 ± 0.3 nM. In HMC-1α155 and FMA3 cells, which carry KIT with mutations in the juxtamembrane domain, the IC50 values were approximately 10 ± 1 nM and 30 ± 1.5 nM, respectively. Masitinib inhibited SCF-stimulated cell proliferation and tyrosine phosphorylation of KIT with an IC50 of 200 ± 50 nM. Masitinib inhibited cell growth and PDGFR phosphorylation in primary and metastatic ISS cell line.

Animal models

Ba/F3 Δ27 tumour model

Dosage form

Oral administration, 30, or 45 mg/kg, twice daily for 10 days

Application

Mice treated with masitinib showed a dose-dependent inhibition of tumour growth. Masitinib at 30 or 45 mg/kg significantly reduced tumour growth following 11 days of treatment compared to placebo, with average tumour volume increases of 355% and 154%, respectively in the masitinib-treated mice. Orally administered masitinib at 100 mg/kg on mice having large Δ27 KIT-expressing tumours. Masitinib (12.5 mg/kg/d, p.o.) increased overall TTP (time-to-tumor progression) compared with placebo in dogs.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Dubreuil P, Letard S, Ciufolini M, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT[J]. PloS one, 2009, 4(9): e7258.

[2]. Lawrence J, Saba C, Gogal R, et al. Masitinib demonstrates anti‐proliferative and pro‐apoptotic activity in primary and metastatic feline injection‐site sarcoma cells[J]. Veterinary and comparative oncology, 2012, 10(2): 143-154.

[3]. Hahn K A, Oglivie G, Rusk T, et al. Masitinib is safe and effective for the treatment of canine mast cell tumors[J]. Journal of Veterinary Internal Medicine, 2008, 22(6): 1301-1309.