Masitinib

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Masitinib
Accession Number
DB11526
Type
Small Molecule
Groups
Investigational, Vet approved
Description

Masitinib is a tyrosine-kinase inhibitor used in the treatment of mast cell tumors in animals, specifically dogs. Since its introduction in November 2008 it has been distributed under the commercial name Masivet. It has been available in Europe since the second part of 2009. In the USA it is distributed under the name Kinavet and has been available for veterinaries since 2011.

Structure
Thumb
Synonyms
  • AB 1010
  • AB-1010
  • AB1010
Product Ingredients
IngredientUNIICASInChI Key
Masitinib mesylateZK89EG3A181048007-93-7TXCWBWKVIZGWEQ-UHFFFAOYSA-N
Categories
UNII
M59NC4E26P
CAS number
790299-79-5
Weight
Average: 498.65
Monoisotopic: 498.220180784
Chemical Formula
C28H30N6OS
InChI Key
WJEOLQLKVOPQFV-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-(4-methyl-3-{[4-(pyridin-3-yl)-2,3-dihydro-1,3-thiazol-2-ylidene]amino}phenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide
SMILES
CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(N=C3NC(=CS3)C3=CN=CC=C3)=C(C)C=C2)CC1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Walker UA: More about masitinib. Arthritis Res Ther. 2009;11(4):120. doi: 10.1186/ar2734. Epub 2009 Jul 13. [PubMed:19664170]
  2. Bellamy F, Bader T, Moussy A, Hermine O: Pharmacokinetics of masitinib in cats. Vet Res Commun. 2009 Dec;33(8):831-7. doi: 10.1007/s11259-009-9231-6. [PubMed:19533403]
  3. 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:21953477]
  4. Daly M, Sheppard S, Cohen N, Nabity M, Moussy A, Hermine O, Wilson H: Safety of masitinib mesylate in healthy cats. J Vet Intern Med. 2011 Mar-Apr;25(2):297-302. doi: 10.1111/j.1939-1676.2011.0687.x. Epub 2011 Feb 11. [PubMed:21314730]
  5. Procoli F: Clinical trial on the efficacy of masitinib in canine IBD. Vet Rec. 2010 Nov 6;167(19):760. doi: 10.1136/vr.c6030. [PubMed:21257519]
  6. Hahn KA, Ogilvie G, Rusk T, Devauchelle P, Leblanc A, Legendre A, Powers B, Leventhal PS, Kinet JP, Palmerini F, Dubreuil P, Moussy A, Hermine O: Masitinib is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med. 2008 Nov-Dec;22(6):1301-9. doi: 10.1111/j.1939-1676.2008.0190.x. Epub 2008 Sep 24. [PubMed:18823406]
  7. Gentilini F: "Masitinib" is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med. 2010 Jan-Feb;24(1):6; author reply 7. [PubMed:20391634]
  8. Thamm DH, Rose B, Kow K, Humbert M, Mansfield CD, Moussy A, Hermine O, Dubreuil P: Masitinib as a chemosensitizer of canine tumor cell lines: a proof of concept study. Vet J. 2012 Jan;191(1):131-4. doi: 10.1016/j.tvjl.2011.01.001. Epub 2011 Feb 17. [PubMed:21333567]
  9. Tebib J, Mariette X, Bourgeois P, Flipo RM, Gaudin P, Le Loet X, Gineste P, Guy L, Mansfield CD, Moussy A, Dubreuil P, Hermine O, Sibilia J: Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study. Arthritis Res Ther. 2009;11(3):R95. doi: 10.1186/ar2740. Epub 2009 Jun 23. [PubMed:19549290]
  10. Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Casteran 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 Sep 30;4(9):e7258. doi: 10.1371/journal.pone.0007258. [PubMed:19789626]
  11. Daigle J, Moussy A, Mansfield CD, Hermine O: Masitinib for the treatment of canine atopic dermatitis: a pilot study. Vet Res Commun. 2010 Jan;34(1):51-63. doi: 10.1007/s11259-009-9332-2. Epub 2009 Dec 23. [PubMed:20033487]
  12. Le Cesne A, Blay JY, Bui BN, Bouche O, Adenis A, Domont J, Cioffi A, Ray-Coquard I, Lassau N, Bonvalot S, Moussy A, Kinet JP, Hermine O: Phase II study of oral masitinib mesilate in imatinib-naive patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST). Eur J Cancer. 2010 May;46(8):1344-51. doi: 10.1016/j.ejca.2010.02.014. Epub 2010 Mar 6. [PubMed:20211560]
  13. Hahn KA, Legendre AM, Shaw NG, Phillips B, Ogilvie GK, Prescott DM, Atwater SW, Carreras JK, Lana SE, Ladue T, Rusk A, Kinet JP, Dubreuil P, Moussy A, Hermine O: Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors. Am J Vet Res. 2010 Nov;71(11):1354-61. doi: 10.2460/ajvr.71.11.1354. [PubMed:21034327]
  14. Piette F, Belmin J, Vincent H, Schmidt N, Pariel S, Verny M, Marquis C, Mely J, Hugonot-Diener L, Kinet JP, Dubreuil P, Moussy A, Hermine O: Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial. Alzheimers Res Ther. 2011 Apr 19;3(2):16. doi: 10.1186/alzrt75. [PubMed:21504563]
  15. 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:21668810]
  16. Holtermann N, Kiupel M, Kessler M, Teske E, Betz D, Hirschberger J: Masitinib monotherapy in canine epitheliotropic lymphoma. Vet Comp Oncol. 2015 Sep 14. doi: 10.1111/vco.12157. [PubMed:26364581]
External Links
KEGG Drug
D10229
ChemSpider
8250179
BindingDB
50355495
ChEBI
63450
ChEMBL
CHEMBL1908391
HET
G65
Wikipedia
Masitinib
ATC Codes
L01XE22 — Masitinib
PDB Entries
5mql

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAsthma Bronchial1
2CompletedTreatmentDisseminated Sclerosis1
2CompletedTreatmentGastro Intestinal Stromal Tumor1
2CompletedTreatmentGastro-intestinal Stromal Tumours1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentPatients With Mastocytosis With Handicap and Bearing Mutations Asp-816-Val (D816V) / Urticaria Pigmentosa1
2CompletedTreatmentPsoriasis1
2CompletedTreatmentRheumatoid Arthritis2
2CompletedTreatmentUrticaria Pigmentosa1
2, 3Active Not RecruitingTreatmentMetastatic Colorectal Cancers1
2, 3TerminatedTreatmentRheumatoid Arthritis1
3TerminatedTreatment2nd Line Metastatic Colorectal Cancer / Metastatic Colorectal Cancers1
3TerminatedTreatmentGastro-intestinal Stromal Tumours1
3Unknown StatusTreatmentGastrointestinal Stromal Tumors1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.012 mg/mLALOGPS
logP3.64ALOGPS
logP3.85ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)9.52ChemAxon
pKa (Strongest Basic)8.17ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.86 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity152.37 m3·mol-1ChemAxon
Polarizability56.01 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-1291000000-f2e2f823b1870c00bb6d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0236920000-165320b13f69ca2a3a29

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Diaminotoluenes / Benzamides / Phenylmethylamines / Aniline and substituted anilines / Benzylamines / Benzoyl derivatives / 2,4-disubstituted thiazoles / N-methylpiperazines / Aralkylamines / Pyridines and derivatives
show 11 more
Substituents
Benzanilide / Diaminotoluene / Benzamide / Benzoic acid or derivatives / Phenylmethylamine / Aniline or substituted anilines / Benzylamine / Benzoyl / 2,4-disubstituted 1,3-thiazole / Aralkylamine
show 28 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
1,3-thiazole, benzamides, pyridines, N-alkylpiperazine (CHEBI:63450)

Drug created on February 26, 2016 10:35 / Updated on November 02, 2018 08:55