MASITINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H30N6OS
Molecular Weight	498.6445
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1ccc(cc1N=c2[nH]c(cs2)-c3cccnc3)NC(=O)c4ccc(cc4)CN5CCN(C)CC5

InChI

InChIKey=WJEOLQLKVOPQFV-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C28H30N6OS
Molecular Weight	498.6445
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ab-science.com/en/corporate-overview/about-masitinib | http://www.ab-science.com/en/human-medicine/masitinib-in-neurodegenerative-disease | http://www.alzforum.org/therapeutics/masitinib

Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases. AB Science is developing masitinib in multiple sclerosis and alzheimer's disease. Masitinib targets kinases, including c-Kit, PDGFR, and Lyn. It is 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Stem cell growth factor receptor 47 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19789626	Inhibitor 7728	200.0 nM [IC50]
Platelet-derived growth factor receptor alpha 26 Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19789626	Inhibitor 7728	540.0 nM [IC50]
Platelet-derived growth factor receptor beta 51 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19789626	Inhibitor 7728	800.0 nM [IC50]
Tyrosine-protein kinase Lyn 4 Target ID: CHEMBL3905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19789626	Inhibitor 7728	510.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Amyotrophic lateral sclerosis 39 Sources: http://adisinsight.springer.com/drugs/800029638 https://www.ncbi.nlm.nih.gov/pubmed/27400786	Primary	Phase III 643	Unknown Approved Use Unknown
Mastocytosis 4 Sources: http://adisinsight.springer.com/drugs/800029638 https://www.ncbi.nlm.nih.gov/pubmed/28069279	Primary	Phase III 643	Unknown Approved Use Unknown
Alzheimer’s disease 261 Sources: http://adisinsight.springer.com/drugs/800029638 http://www.ab-science.com/en/human-medicine/masitinib-in-neurodegenerative-disease	Primary	Phase III 643	Unknown Approved Use Unknown
Multiple sclerosis 95 Sources: http://adisinsight.springer.com/drugs/800029638 http://www.ab-science.com/en/human-medicine/masitinib-in-neurodegenerative-disease	Primary	Phase III 643	Unknown Approved Use Unknown
Asthma 227 Sources: http://adisinsight.springer.com/drugs/800029638 https://clinicaltrials.gov/ct2/show/NCT01449162	Primary	Phase III 643	Unknown Approved Use Unknown
Colorectal cancer 94 Sources: http://adisinsight.springer.com/drugs/800029638 https://clinicaltrials.gov/ct2/show/NCT02605044	Primary	Phase III 643	Unknown Approved Use Unknown
Gastrointestinal stromal tumor 18 Sources: http://adisinsight.springer.com/drugs/800029638 https://clinicaltrials.gov/ct2/show/NCT01694277	Primary	Phase III 643	Unknown Approved Use Unknown
Malignant melanoma 22 Sources: http://adisinsight.springer.com/drugs/800029638 https://clinicaltrials.gov/ct2/show/NCT01280565	Primary	Phase III 643	Unknown Approved Use Unknown
Multiple myeloma 145 Sources: http://adisinsight.springer.com/drugs/800029638 https://clinicaltrials.gov/ct2/show/NCT01470131	Primary	Phase III 643	Unknown Approved Use Unknown
Pancreatic cancer 92 Sources: http://adisinsight.springer.com/drugs/800029638 https://clinicaltrials.gov/ct2/show/NCT00789633	Primary	Phase III 643	Unknown Approved Use Unknown
Rheumatoid arthritis 294 Sources: https://clinicaltrials.gov/ct2/show/NCT01410695	Primary	Phase III 643	Unknown Approved Use Unknown
Dog mast cell tumours 2 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/veterinary/000128/WC500064717.pdf	Primary	Approved 8043	Masivet Approved Use Treatment of non-resectable dog mast cell tumours (Grade 2 or 3) with confirmed mutated c-kit tyrosine kinase receptor. Launch Date 1.22549764E12

PubMed

Title	Date	PubMed
[Gastrointestinal stromal tumors: molecular aspects and therapeutic implications].	2008 Jan	18230576
Masitinib is safe and effective for the treatment of canine mast cell tumors.	2008 Nov-Dec	18823406
More about masitinib.	2009	19664170
Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study.	2009	19549290
Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics.	2009 Aug	19614621
Pharmacokinetics of masitinib in cats.	2009 Dec	19533403
Phase 1 dose-escalation study of oral tyrosine kinase inhibitor masitinib in advanced and/or metastatic solid cancers.	2009 Sep	19541476
Clinically relevant advances in rheumatoid arthritis therapy.	2009 Sep 14	20948712
Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT.	2009 Sep 30	19789626
[New drugs for small animals in 2009].	2010	22215315
c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis.	2010	20181277
Churg and Strauss vasculitis in the course of masitinib treatment: a first report.	2010 Aug	19958320
Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study.	2010 Dec	21108325
Update on the treatment of gastrointestinal stromal tumors (GISTs): role of imatinib.	2010 Feb 4	20161982
Masitinib for the treatment of canine atopic dermatitis: a pilot study.	2010 Jan	20033487
"Masitinib" is safe and effective for the treatment of canine mast cell tumors.	2010 Jan-Feb	20391634
Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer.	2010 Jul	20364428
[Focus on GIST management].	2010 Jun	20483709
Masitinib combined with standard gemcitabine chemotherapy: in vitro and in vivo studies in human pancreatic tumour cell lines and ectopic mouse model.	2010 Mar 4	20209107
Drug-induced minimal change nephropathy in a dog.	2010 Mar-Apr	20136717
Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST).	2010 May	20211560
The complexity of the complicity of mast cells in cancer.	2010 May	20026421
Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors.	2010 Nov	21034327
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Clinical trial on the efficacy of masitinib in canine IBD.	2010 Nov 6	21257519
Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11.	2010 Oct 15	20950418
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011 Oct 30	22037377
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013 Apr 15	23398362

Patents

Sample Use Guides

In Vivo Use Guide

6 mg/kg/day

Route of Administration: Oral

In Vitro Use Guide

In Ba/F3 cells expressing human wild-type Kit, Masitinib inhibits SCF (stem cell factor)-induced cell proliferation with an IC50 of 150 nM, while the IC50 for inhibition of IL-3-stimulated proliferation is at approximately >10 µM. In Ba/F3 cells expressing PDGFRα, Masitinib inhibits PDGF-BB-stimulated proliferation and PDGFRα tyrosine phosphorylation with IC50 of 300 nM.

Substance Class	Chemical Created by `admin` on `Sat Jun 26 00:51:41 UTC 2021` Edited by `admin` on `Sat Jun 26 00:51:41 UTC 2021`
Record UNII	M59NC4E26P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MASITINIB

Official Name

English

MASITINIB [WHO-DD]

Common Name

English

4-((4-METHYLPIPERAZIN-1-YL)METHYL)-N-(4-METHYL-3-((4-PYRIDIN-3-YL-1,3-THIAZOL-2-YL)AMINO)PHENYL)BENZAMIDE

Systematic Name

English

MASITINIB [MI]

Common Name

English

MASITINIB [INN]

Common Name

English

MASITINIB [MART.]

Common Name

English

KINAVET

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1967