Masitinib mesylate

Short Summary : Tyrosine kinase inhibitor

Category : Tyrosine Kinase|PDGFR

Purity : 0.98

CAS Number : 1048007-93-7

Formula : C29H34N6O4S2

Molecular Weight : 594.75

SMILE : CC1=C(NC2=NC(C3=CN=CC=C3)=CS2)C=C(NC(C4=CC=C(CN5CCN(C)CC5)C=C4)=O)C=C1.CS(=O)(O)=O

Solubility : 25℃: DMSO

Storage : Store at -20°C

Description : Description:
IC50 Value: 200±40 nM ( recombinant human wild-type KIT); 540±60 (PDGFRα) [1]
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.
in vitro: Masitinib inhibited the recombinant enzyme with a half inhibitory concentration (IC50) of 200±40 nM. Kinetic studies in which ATP and masitinib were covaried showed that at concentrations ≤500 nM masitinib is a competitive inhibitor against ATP, but at higher concentrations (>1 M), it has a mixed mechanism of inhibition against ATP. Under identical assay conditions and with the same enzyme, imatinib had an IC50 of 470±120 nM and was a strictly competitive inhibitor against ATP. Masitinib only weakly inhibited the proliferation of Ba/F3 cells expressing the D816V mutant of KIT, which is associated with adult mastocytosis and myeloproliferative disorder-acute myeloid leukaemia (exon 17), with an IC50 of 5.0±2.0 M [1]. The 50% inhibitory concentration (IC(50) ) at 72 h for three HSA cell lines (DEN, Fitz and SB) was found to be 8.56, 9.41 and 10.65 M, respectively. Further investigation demonstrated that masitinib mesylate induced apoptosis in all HSA cell lines, including activation of caspase-3/7. Measurement of VEGF levels in cell supernatant found a statistically significant increased VEGF in close proximity to the IC(50) of each cell line followed by a decline back towards baseline [2].
in vivo: Masitinib appeared to have a positive effect on MS-related impairment for PPMS and rfSPMS patients, as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in patients receiving placebo; +103% ± 189 versus -60% ± 190 at month-12, respectively [3]. A reduction in CAD Extent and Severity Index (CADESI-02) score of ≥ 50% at week 12 was observed in 61% of masitinib-treated dogs versus 35% of control dogs (P < 0.001), according to the modified intent-to-treat population [4].
Toxicity: Clinically relevant proteinuria was noted in 2/20 (10%) cats (both treated daily), and neutropenia was noted in 3/20 (15%) (seen in both treatment groups). An increase in serum creatinine concentration and adverse gastrointestinal effects were noted in some cats [5].
Clinical trial: N/A

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