| Masitinib (AB1010)Tyrosine kinase inhibitor, potent and selective |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
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- Purity = 99.60%
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Chemical structure
| Description | Masitinib is a potent and selective inhibitor of tyrosine kinases with IC50 values of 200 nM, 540 nM and 800 nM for KIT, PDGFRα and PDGFRβ, respectively. | |||||
| Targets | KIT | PDGFRα | PDGFRβ | |||
| IC50 | 200 nM | 540 nM | 800 nM | |||
| Cell experiment [1,2]: | |
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 experiment [1,3]: | |
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. | |
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| Cas No. | 790299-79-5 | SDF | Download SDF |
| Chemical Name | 4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide | ||
| Canonical SMILES | CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC(=CS4)C5=CN=CC=C5 | ||
| Formula | C28H30N6OS | M.Wt | 498.64 |
| Solubility | ≥24.95mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
The stem cell factor receptor (KIT) is a therapeutic target for the cancer, mastocytosis, and inflammatory diseases treatment. Masitinib (AB1010) is a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT.In vitro: Masitinib potently inhibited the intracellular kinase Lyn and recombinant PDGFR as well as fibroblast growth factor receptor 3. Moreover, masitinib showed weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. These findings suggest that Masitinib (AB1010) will exhibit a better safety profile than other tyrosine kinase inhibitors; in fact, masitinib-induced genotoxicity or cardiotoxicity has not been observed in animal so far [1]. In vivo: In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. We found that tumour growth was blocked following 5 days of treatment with masitinib. After withdrawal of masitinib treatment after day 5, tumour growth was once again evident [1]. Clinical trial: A Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST). Thirty patients were enrolled with a median follow-up of 34 months. Masitinib appears to be effective as a first-line treatment of advanced GIST with comparable results to imatinib in terms of safety and response. PFS and OS results data show promise that masitinib may provide sustainable benefits [2].Reference:[1] Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W, Voisset E, Arock M, Auclair C, Leventhal PS, Mansfield CD, Moussy A, Hermine O. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One. 2009;4(9):e7258. [2] Sylvie Bonvalot , Alain Moussy , Jean-Pierre Kinet , et al. Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST). European Journal of Cancer. 2010(46): 1344-1351
