Masitinib

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WARNING: This product is for research use only, not for human or veterinary use.

Description:Masitinib, also known as AB1010, is an orally bioavailable and multi-targeted protein tyrosine kinase inhibitor with potential antineoplastic activity. Masitinib selectively binds to and inhibits both the wild-type and mutated forms of the stem cell factor receptor (c-Kit; SCFR); platelet-derived growth factor receptor (PDGFR); fibroblast growth factor receptor 3 (FGFR3); and, to a lesser extent, focal adhesion kinase (FAK). As a consequence, tumor cell proliferation may be inhibited in cancer cell types that overexpress these receptor tyrosine kinases (RTKs). Masitinib was approved for veterinary use.

Price and Availability

Masitinib (free base), purity > 99%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201804Name: MasitinibCAS#: 790299-79-5Chemical Formula: C28H30N6OSExact Mass: 498.22018Molecular Weight: 498.64Elemental Analysis:C, 67.44; H, 6.06; N, 16.85; O, 3.21; S, 6.43

Synonym:AB-1010; AB 1010; AB1010; Masitinib. Brand name: Kinavet; Masivet.

IUPAC/Chemical Name:4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)-1,3-thiazol-2-yl]amino}phenyl)benzamide

InChi Key:WJEOLQLKVOPQFV-UHFFFAOYSA-N

InChi Code:InChI=1S/C28H30N6OS/c1-20-5-10-24(16-25(20)31-28-32-26(19-36-28)23-4-3-11-29-17-23)30-27(35)22-8-6-21(7-9-22)18-34-14-12-33(2)13-15-34/h3-11,16-17,19H,12-15,18H2,1-2H3,(H,30,35)(H,31,32)

SMILES Code:O=C(NC1=CC=C(C)C(NC2=NC(C3=CC=CN=C3)=CS2)=C1)C4=CC=C(CN5CCN(C)CC5)C=C4

Technical Data

Additional Information

 Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicity. Phase II clinical trials demonstrate that 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 in particular OS data show promise that masitinib may provide sustainable benefits. There is sufficient compelling evidence to warrant a phase III clinical trial. see http://www.ncbi.nlm.nih.gov/pubmed/20211560.  

References

1: Kocic I, Kowianski P, Rusiecka I, Lietzau G,Mansfield C, Moussy A, Hermine O, Dubreuil P. Neuroprotective effect ofmasitinib in rats with postischemic stroke. Naunyn Schmiedebergs ArchPharmacol. 2015 Jan;388(1):79-86. doi: 10.1007/s00210-014-1061-6. Epub2014 Oct 26. PubMed PMID: 25344204; PubMed Central PMCID: PMC4284372.

2: Adenis A, Blay JY, Bui-Nguyen B, Bouché O, Bertucci F, Isambert N,Bompas E, Chaigneau L, Domont J, Ray-Coquard I, Blésius A, Van Tine BA,Bulusu VR, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, LeCesne A. Masitinib in advanced gastrointestinal stromal tumor (GIST)after failure of imatinib: a randomized controlled open-label trial. AnnOncol. 2014 Sep;25(9):1762-9. doi: 10.1093/annonc/mdu237. Epub 2014 Jul25. PubMed PMID: 25122671; PubMed Central PMCID: PMC4143095.

3: Rathore K, Alexander M, Cekanova M. Piroxicam inhibits Masitinib-inducedcyclooxygenase 2 expression in oral squamous cell carcinoma cells invitro. Transl Res. 2014 Aug;164(2):158-68. doi:10.1016/j.trsl.2014.02.002. Epub 2014 Feb 21. PubMed PMID: 24631063.

4: Kathawala RJ, Chen JJ, Zhang YK, Wang YJ, Patel A, Wang DS, TaleleTT, Ashby CR Jr, Chen ZS. Masitinib antagonizes ATP-binding cassettesubfamily G member 2-mediated multidrug resistance. Int J Oncol. 2014May;44(5):1634-42. doi: 10.3892/ijo.2014.2341. Epub 2014 Mar 13. PubMedPMID: 24626598; PubMed Central PMCID: PMC4027943.

5: Turek M, Gogal R Jr, Saba C, Vandenplas ML, Hill J, Feldhausser B,Lawrence J. Masitinib mesylate does not enhance sensitivity to radiationin three feline injection-site sarcoma cell lines under normal growthconditions. Res Vet Sci. 2014 Apr;96(2):304-7. doi:10.1016/j.rvsc.2014.02.001. Epub 2014 Feb 11. PubMed PMID: 24602916.

6: Kathawala RJ, Sodani K, Chen K, Patel A, Abuznait AH, Anreddy N, SunYL, Kaddoumi A, Ashby CR Jr, Chen ZS. Masitinib antagonizes ATP-bindingcassette subfamily C member 10-mediated paclitaxel resistance: apreclinical study. Mol Cancer Ther. 2014 Mar;13(3):714-23. doi:10.1158/1535-7163.MCT-13-0743. Epub 2014 Jan 15. PubMed PMID: 24431074;PubMed Central PMCID: PMC3954439.

7: Marech I, Patruno R, Zizzo N, Gadaleta C, Introna M, Zito AF,Gadaleta CD, Ranieri G. Masitinib (AB1010), from canine tumor model tohuman clinical development: where we are? Crit Rev Oncol Hematol. 2014Jul;91(1):98-111. doi: 10.1016/j.critrevonc.2013.12.011. Epub 2013 Dec17. Review. PubMed PMID: 24405856.

8: Avula MN, Rao AN, McGill LD, Grainger DW, Solzbacher F. Modulation ofthe foreign body response to implanted sensor models throughdevice-based delivery of the tyrosine kinase inhibitor, masitinib.Biomaterials. 2013 Dec;34(38):9737-46. doi:10.1016/j.biomaterials.2013.08.090. Epub 2013 Sep 20. PubMed PMID:24060424.

9: Brown MR, Cianciolo RE, Nabity MB, Brown CA, Clubb FJ, Lees GE.Masitinib-associated minimal change disease with acute tubular necrosisresulting in acute kidney injury in a dog. J Vet Intern Med. 2013Nov-Dec;27(6):1622-6. doi: 10.1111/jvim.12189. Epub 2013 Sep 10. PubMedPMID: 24020652.

10: Smrkovski OA, Essick L, Rohrbach BW, Legendre AM. Masitinib mesylatefor metastatic and non-resectable canine cutaneous mast cell tumours.Vet Comp Oncol. 2013 Jul 12. doi: 10.1111/vco.12053. [Epub ahead ofprint] PubMed PMID: 23845124.

11: Fahey CE, Milner RJ, Kow K, Bacon NJ, Salute ME. Apoptotic effectsof the tyrosine kinase inhibitor, masitinib mesylate, on canineosteosarcoma cells. Anticancer Drugs. 2013 Jun;24(5):519-26. doi:10.1097/CAD.0b013e32836002ba. PubMed PMID: 23466652.

12: Zandvliet M, Teske E, Chapuis T, Fink-Gremmels J, Schrickx JA.Masitinib reverses doxorubicin resistance in canine lymphoid cells byinhibiting the function of P-glycoprotein. J Vet Pharmacol Ther. 2013Dec;36(6):583-7. doi: 10.1111/jvp.12039. Epub 2013 Jan 31. PubMed PMID:23363222.

13: Vermersch P, Benrabah R, Schmidt N, Zéphir H, Clavelou P, VongsouthiC, Dubreuil P, Moussy A, Hermine O. Masitinib treatment in patients withprogressive multiple sclerosis: a randomized pilot study. BMC Neurol.2012 Jun 12;12:36. doi: 10.1186/1471-2377-12-36. PubMed PMID: 22691628;PubMed Central PMCID: PMC3467179.

14: Lyles SE, Milner RJ, Kow K, Salute ME. In vitro effects of thetyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcomacell lines. Vet Comp Oncol. 2012 Sep;10(3):223-35. doi:10.1111/j.1476-5829.2012.00335.x. Epub 2012 May 18. PubMed PMID:22594682.

15: Lee-Fowler TM, Guntur V, Dodam J, Cohn LA, DeClue AE, Reinero CR.The tyrosine kinase inhibitor masitinib blunts airway inflammation andimproves associated lung mechanics in a feline model of chronic allergicasthma. Int Arch Allergy Immunol. 2012;158(4):369-74. doi:10.1159/000335122. Epub 2012 Apr 4. PubMed PMID: 22487554.

16: Georgin-Lavialle S, Lhermitte L, Suarez F, Yang Y, Letard S,Hanssens K, Feger F, Renand A, Brouze C, Canioni D, Asnafi V, ChandesrisMO, Aouba A, Gineste P, Macintyre E, Mansfield CD, Moussy A, LepelletierY, Dubreuil P, Hermine O. Mast cell leukemia: identification of a newc-Kit mutation, dup(501-502), and response to masitinib, a c-Kittyrosine kinase inhibitor. Eur J Haematol. 2012 Jul;89(1):47-52. doi:10.1111/j.1600-0609.2012.01761.x. Epub 2012 Apr 28. PubMed PMID:22324351.

17: Lawrence J, Saba C, Gogal R Jr, Lamberth O, Vandenplas ML, HurleyDJ, Dubreuil P, Hermine O, Dobbin K, Turek M. Masitinib demonstratesanti-proliferative and pro-apoptotic activity in primary and metastaticfeline injection-site sarcoma cells. Vet Comp Oncol. 2012Jun;10(2):143-54. doi: 10.1111/j.1476-5829.2011.00291.x. Epub 2011 Aug25. PubMed PMID: 22236016.

18: Moura DS, Sultan S, Georgin-Lavialle S, Pillet N, Montestruc F,Gineste P, Barete S, Damaj G, Moussy A, Lortholary O, Hermine O.Depression in patients with mastocytosis: prevalence, features andeffects of masitinib therapy. PLoS One. 2011;6(10):e26375. doi:10.1371/journal.pone.0026375. Epub 2011 Oct 21. PubMed PMID: 22031830;PubMed Central PMCID: PMC3198767.

19: Chaigne B, Lagier L, Aubourg A, de Muret A, Jonville-Bera AP, MachetL, Samimi M. Stevens-Johnson Syndrome induced by masitinib. Acta DermVenereol. 2012 Mar;92(2):210-2. doi: 10.2340/00015555-1196. PubMed PMID:21953477.

20: Cadot P, Hensel P, Bensignor E, Hadjaje C, Marignac G, Beco L,Fontaine J, Jamet JF, Georgescu G, Campbell K, Cannon A, Osborn SC,Messinger L, Gogny-Goubert M, Dubreuil P, Moussy A, Hermine O. Masitinibdecreases signs of canine atopic dermatitis: a multicentre, randomized,double-blind, placebo-controlled phase 3 trial. Vet Dermatol. 2011Dec;22(6):554-64. doi: 10.1111/j.1365-3164.2011.00990.x. Epub 2011 Jun13. PubMed PMID: 21668810.