Masitinib

Masitinib
Clinical data

Trade names	Masivet, Kinavet
AHFS/Drugs.com	International Drug Names
ATC code	L01XE22 (WHO)
Identifiers
IUPAC name 4-[(4-Methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)-1,3-thiazol-2-yl]amino}phenyl)benzamide
CAS Number	790299-79-5
PubChem (CID)	10074640
ChemSpider	8250179
ChEMBL	CHEMBL1908391
Chemical and physical data
Formula	C₂₈H₃₀N₆OS
Molar mass	498.64 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(c1ccc(cc1)CN2CCN(C)CC2)Nc3cc(c(cc3)C)Nc4nc(cs4)c5cccnc5
InChI InChI=InChI=1S/C28H30N6OSc1-20-5-10-24(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)13-15-34h3-11,16-17,19H,12-15,18H2,1-2H3,(H,30,35)(H,31,32) Key:WJEOLQLKVOPQFV-UHFFFAOYSA-N

Masitinib is a tyrosine-kinase inhibitor used in the treatment of mast cell tumors in animals, specifically dogs.^[1]^[2] 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.

Masitinib is being studied for several human conditions including cancers and Amyotrophic lateral sclerosis.^[3]^[4] It is used in Europe for orphan diseases.^[5]

Mechanism of action

Masitinib inhibits the receptor tyrosine kinase c-Kit which is displayed by various types of tumour.^[2] It also inhibits the platelet derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR).

References

↑ Hahn, K.A.; Oglivie, G.; Rusk, T.; Devauchelle, P.; Leblanc, A.; Legendre, A.; Powers, B.; Leventhal, P.S.; Kinet, J.-P.; Palmerini, F.; Dubreuil, P.; Moussy, A.; Hermine, O. (2008). "Masitinib is Safe and Effective for the Treatment of Canine Mast Cell Tumors". Journal of Veterinary Internal Medicine. 22 (6): 1301–1309. doi:10.1111/j.1939-1676.2008.0190.x. ISSN 0891-6640.
1 2 Information about Masivet at the European pharmacy agency website
↑ https://clinicaltrials.gov/ct2/show/NCT02588677
↑ http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2016/10/human_orphan_001821.jsp
↑ Orphan designation for Masitinib at the European pharmacy agency website

Targeted therapy / extracellular chemotherapeutic agents/antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Cetuximab Panitumumab) HER2/neu (Trastuzumab Trastuzumab emtansine)

Others for solid tumors	EpCAM (Catumaxomab Edrecolomab) VEGF-A (Bevacizumab)

Leukemia/lymphoma	lymphoid: CD20 (Ibritumomab Ofatumumab Rituximab Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab) myeloid: CD33 (Gemtuzumab)

Tyrosine-kinase inhibitors ("-nib")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Erlotinib Gefitinib Osimertinib Vandetanib) HER1/EGFR and HER2/neu Afatinib Lapatinib Neratinib RTK class III: C-kit and PDGFR (Axitinib Masitinib Pazopanib Sunitinib Sorafenib Toceranib) FLT3 (Lestaurtinib) VEGFR Axitinib Cediranib Lenvatinib Nintedanib Pazopanib Regorafenib Semaxanib Sorafenib Sunitinib Tivozanib Toceranib Vandetanib RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2).

Non-receptor	bcr-abl Imatinib Dasatinib Nilotinib Ponatinib Radotinib Src (Bosutinib) Janus kinase Lestaurtinib Momelotinib Ruxolitinib Pacritinib MAP2K Cobimetinib Selumetinib Trametinib Binimetinib EML4-ALK Alectinib Ceritinib Crizotinib Bruton's (Ibrutinib)

Other

fusion protein against VEGF (Aflibercept)
proapoptotic peptide against ANXA2 and prohibitin (Adipotide)
exotoxin against IL-2 (Denileukin diftitox)
mTOR inhibitors
- Everolimus
- Temsirolimus
hedgehog inhibitors
- Sonidegib
- Vismodegib
CDK inhibitor (Palbociclib)

Growth factor receptor modulators

Angiopoietin

Agonists: Angiopoietin 1
Angiopoietin 4

Antagonists: Angiopoietin 2
Angiopoietin 3

Antibodies: Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

Agonists: Axokine
CNTF
Dapiclermin

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists: Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab Kinase inhibitors: Afatinib AG-490 Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154

ErbB2/HER2	Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib AG-490 Lapatinib Mubritinib Neratinib

ErbB3/HER3	Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C)) Antibodies: Duligotumab Patritumab Seribantumab

ErbB4/HER4	Agonists: Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20) Repifermin Trafermin Velafermin

FGFR2	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22) Palifermin Repifermin Sprifermin Trafermin Antibodies: Aprutumab Aprutumab ixadotin

FGFR3	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 8, 9, 18, 23) Sprifermin Trafermin Antibodies: Burosumab (against FGF23)

FGFR4	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 6, 8, 9, 19) Trafermin

Unsorted	Agonists: FGF15/19

HGF (c-Met)

Agonists: Hepatocyte growth factor

Potentiators: Dihexa (PNB-0408)

Antibodies: Emibetuzumab
Ficlatuzumab
Flanvotumab
Onartuzumab
Rilotumumab
Telisotuzumab
Telisotuzumab vedotin

Kinase inhibitors: AM7 (drug)
AMG-458
Amuvatinib
BMS-777607
Cabozantinib
Crizotinib
Foretinib
Golvatinib
INCB28060
JNJ-38877605
K252a
MK-2461
PF-04217903
PF-2341066
PHA-665752
SU-11274
Tivantinib
Volitinib

IGF

IGF-1	Agonists: des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Antagonists: BMS-754807 Antibodies: AVE1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Kinase inhibitors: Linsitinib NVP-ADW742 NVP-AEW541 OSl-906

IGF-2	Agonists: Insulin-like growth factor-2 (somatomedin A) Antibodies: Dusigitumab

Others	Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7) Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF

Agonists: BDNF
Cenegermin
NGF
NT-3
NT-4

Antagonists: SAR127963

Antibodies: Against NGF: Fasinumab
Fulranumab
Ranevetmab
Tanezumab

PDGF

Agonists: Becaplermin
Platelet-derived growth factor (A, B, C, D)

RET (GFL)

GFRα1	Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib

GFRα2	Agonists: Neurturin (NRTN) Kinase inhibitors: Vandetanib

GFRα3	Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib

GFRα4	Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib

Unsorted	Kinase inhibitors: Agerafenib

SCF (c-Kit)

Agonists: Ancestim
Stem cell factor

TGFβ

See here instead.

Trk

TrkA	Agonists: Amitriptyline Cenegermin Gambogic amide NGF Tavilermide Antagonists: FX007 Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101 Antibodies: Against NGF: Fasinumab Fulranumab Ranevetmab Tanezumab

TrkB	Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF Deoxygedunin Diosmetin HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 TDP6 Antagonists: ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101

TrkC	Agonists: NT-3 Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101

VEGF

Agonists: Placental growth factor (PGF)
Telbermin
VEGF (A, B, C, D (FIGF))

Allosteric modulators: Cyclotraxin B

Decoy receptors: Aflibercept

Others

Additional growth factors: Adrenomedullin
Colony-stimulating factors (see here instead)
Connective tissue growth factor (CTGF)
Ephrins (A1, A2, A3, A4, A5, B1, B2, B3)
Erythropoietin (see here instead)
Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
Glia maturation factor (GMF)
Hepatoma-derived growth factor (HDGF)
Interleukins/T-cell growth factors (see here instead)
Leukemia inhibitory factor (LIF)
Macrophage-stimulating protein (MSP; HLP, HGFLP)
Midkine (NEGF2)
Migration-stimulating factor (MSF; PRG4)
Oncomodulin
Pituitary adenylate cyclase-activating peptide (PACAP)
Pleiotrophin
Renalase
Thrombopoietin (see here instead)
Wnt signaling proteins

Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)

See also: Peptide receptor modulators
Cytokine receptor modulators

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