Masitinib
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This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
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Identification
- Generic Name
- Masitinib
- DrugBank Accession Number
- DB11526
- Background
Masitinib is a tyrosine-kinase inhibitor used in the treatment of mast cell tumors in dogs. It has been available in Europe since 2009, under the brand name Masivet. In the USA it is distributed under the name Kinavet and has been available for veterinaries since 2011.
- Type
- Small Molecule
- Groups
- Investigational, Vet approved
- Structure
- Weight
- Average: 498.65
Monoisotopic: 498.220180784 - Chemical Formula
- C28H30N6OS
- Synonyms
- 4-((4-METHYLPIPERAZIN-1-YL)METHYL)-N-(4-METHYL-3-((4-PYRIDIN-3-YL-1,3-THIAZOL-2-YL)AMINO)PHENYL)BENZAMIDE
- Masitinib
- External IDs
- AB 1010
- AB-1010
- AB1010
Pharmacology
- Indication
Not Available
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- Pharmacodynamics
Not Available
- Mechanism of action
Target Actions Organism AProto-oncogene tyrosine-protein kinase Src inhibitorHumans - 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Masitinib is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Masitinib is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Masitinib is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Masitinib is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Masitinib is combined with Bupivacaine. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Masitinib mesylate ZK89EG3A18 1048007-93-7 TXCWBWKVIZGWEQ-UHFFFAOYSA-N - International/Other Brands
- Kinavet / Masivet
Categories
- ATC Codes
- L01EX06 — Masitinib
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- 1,3-thiazol-2-amine / 1,4-diazinane / 2,4-disubstituted 1,3-thiazole / Amine / Amino acid or derivatives / Aniline or substituted anilines / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Azole show 28 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- 1,3-thiazole, benzamides, pyridines, N-alkylpiperazine (CHEBI:63450)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- M59NC4E26P
- CAS number
- 790299-79-5
- 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)-1,3-thiazol-2-yl]amino}phenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide
- SMILES
- CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC=C(C)C(NC3=NC(=CS3)C3=CN=CC=C3)=C2)CC1
References
- General References
- Walker UA: More about masitinib. Arthritis Res Ther. 2009;11(4):120. doi: 10.1186/ar2734. Epub 2009 Jul 13. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- Human Metabolome Database
- HMDB0254344
- KEGG Drug
- D10229
- ChemSpider
- 8250179
- BindingDB
- 50355495
- ChEBI
- 63450
- ChEMBL
- CHEMBL1908391
- ZINC
- ZINC000034177219
- PDBe Ligand
- G65
- Wikipedia
- Masitinib
- PDB Entries
- 5mql / 7ju7 / 7tvx
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Alzheimer's Disease (AD) 1 somestatus stop reason just information to hide 3 Completed Treatment Asthma 2 somestatus stop reason just information to hide 3 Completed Treatment Gastrointestinal Stromal Tumor (GIST) 1 somestatus stop reason just information to hide 3 Completed Treatment Locally Advanced or Metastatic Pancreatic Cancer 1 somestatus stop reason just information to hide 3 Completed Treatment Mastocytosis, Indolent Systemic 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.00289 mg/mL ALOGPS logP 4.18 ALOGPS logP 4.97 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 15.12 Chemaxon pKa (Strongest Basic) 7.84 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 73.39 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 147 m3·mol-1 Chemaxon Polarizability 55.33 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 208.7431 predictedDeepCCS 1.0 (2019) [M+H]+ 211.13866 predictedDeepCCS 1.0 (2019) [M+Na]+ 217.05118 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14585963, PubMed:8755529). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances RIGI-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028)
- Specific Function
- ATP binding
- Gene Name
- SRC
- Uniprot ID
- P12931
- Uniprot Name
- Proto-oncogene tyrosine-protein kinase Src
- Molecular Weight
- 59834.295 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at February 26, 2016 17:35 / Updated at August 26, 2024 19:23