Masitinib
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MedKoo CAT#: 201804

CAS#: 790299-79-5

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.


Chemical Structure

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Masitinib
CAS# 790299-79-5

Theoretical Analysis

MedKoo Cat#: 201804
Name: Masitinib
CAS#: 790299-79-5
Chemical Formula: C28H30N6OS
Exact Mass: 498.22018
Molecular Weight: 498.64
Elemental Analysis: C, 67.44; H, 6.06; N, 16.85; O, 3.21; S, 6.43

Price and Availability

Size Price Availability Quantity
100.0mg USD 150.0 Same day
200.0mg USD 250.0 Same day
500.0mg USD 450.0 Same day
1.0g USD 750.0 Same day
2.0g USD 900.0 Same day
5.0g USD 1550.0 Same day
10.0g USD 2650.0 Same day
20.0g USD 3950.0 2 Weeks
50.0g USD 4950.0 2 Weeks
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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

Appearance: Off-white to pale yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Masitinib (AB1010) is an inhibitor of c-Kit with an IC50 of 200 nM for human recombinant c-Kit.
In vitro activity: Masitinib, a drug originally developed as a tyrosine-kinase inhibitor for cancer treatment, strongly inhibited the activity of the SARS-CoV-2 main protease 3CLpro. X-ray crystallography revealed that masitinib directly binds to the active site of 3CLpro, thereby blocking its enzymatic activity. Mastinib also inhibited the related viral protease of picornaviruses and blocked picornaviruses replication. These results show that masitinib has broad anti-viral activity against two distinct beta-coronaviruses and multiple picornaviruses that cause human disease and is a strong candidate for clinical trials to treat SARS-CoV-2 infection. Reference: bioRxiv. 2020 Sep 1:2020.08.31.274639. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480023/
In vivo activity: Chronic oral treatment of APPswe/PSEN1dE9 transgenic mice modeling Alzheimer's disease with masitinib restored normal spatial learning performance while having no impacts on amyloid-β loads nor on neuroinflammation. However, masitinib promoted a recovery of synaptic markers. Complete genetic depletion of mast cells in APPswe/PSEN1dE9 mice similarly rescued synaptic impairments. These results underline that masitinib therapeutic efficacy might primarily be associated with a synapto-protective action in relation with mast cells inhibition. Reference: J Alzheimers Dis. 2020;76(4):1339-1345. https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200466

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 10.0 20.05

Preparing Stock Solutions

The following data is based on the product molecular weight 498.64 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Drayman N, Jones KA, Azizi SA, Froggatt HM, Tan K, Maltseva NI, Chen S, Nicolaescu V, Dvorkin S, Furlong K, Kathayat RS, Firpo MR, Mastrodomenico V, Bruce EA, Schmidt MM, Jedrzejczak R, Muñoz-Alía MÁ, Schuster B, Nair V, Botten JW, Brooke CB, Baker SC, Mounce BC, Heaton NS, Dickinson BC, Jaochimiak A, Randall G, Tay S. Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2 in vitro. bioRxiv [Preprint]. 2020 Sep 1:2020.08.31.274639. doi: 10.1101/2020.08.31.274639. PMID: 32908976; PMCID: PMC7480023. 2. Li T, Martin E, Abada YS, Boucher C, Cès A, Youssef I, Fenaux G, Forand Y, Legrand A, Nachiket N, Dhenain M, Hermine O, Dubreuil P, Delarasse C, Delatour B. Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease. J Alzheimers Dis. 2020;76(4):1339-1345. doi: 10.3233/JAD-200466. PMID: 32623401.
In vitro protocol: 1. Drayman N, Jones KA, Azizi SA, Froggatt HM, Tan K, Maltseva NI, Chen S, Nicolaescu V, Dvorkin S, Furlong K, Kathayat RS, Firpo MR, Mastrodomenico V, Bruce EA, Schmidt MM, Jedrzejczak R, Muñoz-Alía MÁ, Schuster B, Nair V, Botten JW, Brooke CB, Baker SC, Mounce BC, Heaton NS, Dickinson BC, Jaochimiak A, Randall G, Tay S. Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2 in vitro. bioRxiv [Preprint]. 2020 Sep 1:2020.08.31.274639. doi: 10.1101/2020.08.31.274639. PMID: 32908976; PMCID: PMC7480023.
In vivo protocol: 1. Li T, Martin E, Abada YS, Boucher C, Cès A, Youssef I, Fenaux G, Forand Y, Legrand A, Nachiket N, Dhenain M, Hermine O, Dubreuil P, Delarasse C, Delatour B. Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease. J Alzheimers Dis. 2020;76(4):1339-1345. doi: 10.3233/JAD-200466. PMID: 32623401.

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1: Kocic I, Kowianski P, Rusiecka I, Lietzau G, Mansfield C, Moussy A, Hermine O, Dubreuil P. Neuroprotective effect of masitinib in rats with postischemic stroke. Naunyn Schmiedebergs Arch Pharmacol. 2015 Jan;388(1):79-86. doi: 10.1007/s00210-014-1061-6. Epub 2014 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, Le Cesne A. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol. 2014 Sep;25(9):1762-9. doi: 10.1093/annonc/mdu237. Epub 2014 Jul 25. PubMed PMID: 25122671; PubMed Central PMCID: PMC4143095.

3: Rathore K, Alexander M, Cekanova M. Piroxicam inhibits Masitinib-induced cyclooxygenase 2 expression in oral squamous cell carcinoma cells in vitro. 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, Talele TT, Ashby CR Jr, Chen ZS. Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance. Int J Oncol. 2014 May;44(5):1634-42. doi: 10.3892/ijo.2014.2341. Epub 2014 Mar 13. PubMed PMID: 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 radiation in three feline injection-site sarcoma cell lines under normal growth conditions. 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, Sun YL, Kaddoumi A, Ashby CR Jr, Chen ZS. Masitinib antagonizes ATP-binding cassette subfamily C member 10-mediated paclitaxel resistance: a preclinical 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 to human clinical development: where we are? Crit Rev Oncol Hematol. 2014 Jul;91(1):98-111. doi: 10.1016/j.critrevonc.2013.12.011. Epub 2013 Dec 17. Review. PubMed PMID: 24405856.

8: Avula MN, Rao AN, McGill LD, Grainger DW, Solzbacher F. Modulation of the foreign body response to implanted sensor models through device-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 necrosis resulting in acute kidney injury in a dog. J Vet Intern Med. 2013 Nov-Dec;27(6):1622-6. doi: 10.1111/jvim.12189. Epub 2013 Sep 10. PubMed PMID: 24020652.

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

11: Fahey CE, Milner RJ, Kow K, Bacon NJ, Salute ME. Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma 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 by inhibiting the function of P-glycoprotein. J Vet Pharmacol Ther. 2013 Dec;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, Vongsouthi C, Dubreuil P, Moussy A, Hermine O. Masitinib treatment in patients with progressive 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 the tyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcoma cell 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 and improves associated lung mechanics in a feline model of chronic allergic asthma. 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, Chandesris MO, Aouba A, Gineste P, Macintyre E, Mansfield CD, Moussy A, Lepelletier Y, Dubreuil P, Hermine O. Mast cell leukemia: identification of a new c-Kit mutation, dup(501-502), and response to masitinib, a c-Kit tyrosine 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, Hurley DJ, Dubreuil P, Hermine O, Dobbin K, Turek M. Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells. Vet Comp Oncol. 2012 Jun;10(2):143-54. doi: 10.1111/j.1476-5829.2011.00291.x. Epub 2011 Aug 25. 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 and effects 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, Machet L, Samimi M. Stevens-Johnson Syndrome induced by masitinib. Acta Derm Venereol. 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. Masitinib decreases signs of canine atopic dermatitis: a multicentre, randomized, double-blind, placebo-controlled phase 3 trial. Vet Dermatol. 2011 Dec;22(6):554-64. doi: 10.1111/j.1365-3164.2011.00990.x. Epub 2011 Jun 13. PubMed PMID: 21668810.

Masitinib

100.0mg / USD 150.0


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.