| Identification | Back Directory | [Name]
Toceranib | [CAS]
356068-94-5 | [Synonyms]
CS-1158
SU-11654
Toceranib
PHA 291639
Toceranib-d8
Toceranib(SU 11654
Toceranib free base
Toceranib,PHA-291639
Toceranib
DISCONTINUED
TOCERANIB;SU 11654;PHA 291639
Toceranib (PHA 291639, SU 11654)
SU 11654; PHA 291639; SU11654; SU-11654; PHA-291639; PHA291639
5-HYDROXY-2-(4-HYDROXY-3-METHOXYPHENYL)-7-METHOXY-4H-CHROMEN-4-ONE
(Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-N-(2-(pyrrolidin-1-yl)ethyl)-1H-p
(Z)-5-(5-Fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidenemethyl)-2,4-dimethyl-N-[2-(1-pyrrolidinyl)ethyl]-1H-pyrrole-3-carboxamide
(Z)-5-[(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-(2-pyrrolidin-1-ylethyl)-1H-pyrrole-3-carboxamide
5-[(Z)-(5-Fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)Methyl]-2,4-diMethyl-N-[2-(1-pyrrolidinyl)ethyl]-1H-pyrrole-3-carboxaMide
5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrol-3-carboxamide
5-(5-Fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylideneMethyl)-2,4-diMethyl-1H-pyrrole-3-carboxylic Acid (2-(Pyrrolidin-1-yl)ethyl)aMide
1H-Pyrrole-3-carboxaMide, 5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)Methyl]-2,4-diMethyl-N-[2-(1-pyrrolidinyl)ethyl]-
5-[(Z)-(5-Fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)Methyl]-2,4-diMethyl-N-[2-(1-pyrrolidinyl-d8)ethyl]-1H-pyrrole-3-carboxaMide
5-(5-Fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylideneMethyl)-2,4-diMethyl-1H-pyrrole-3-carboxylic Acid (2-(Pyrrolidin-1-yl-d8)ethyl)aMide | [Molecular Formula]
C22H25FN4O2 | [MDL Number]
MFCD16038046 | [MOL File]
356068-94-5.mol | [Molecular Weight]
396.46 |
| Chemical Properties | Back Directory | [Melting point ]
>133°C (dec.) | [Boiling point ]
596.8±50.0 °C(Predicted) | [density ]
1.293 | [storage temp. ]
room temp | [solubility ]
DMSO (Slightly, Heated), Methanol (Very Slightly, Heated) | [form ]
powder | [pka]
11.70±0.20(Predicted) | [color ]
yellow to orange | [InChIKey]
SRSGVKWWVXWSJT-ATVHPVEESA-N | [SMILES]
Fc1cc2c(cc1)NC(=O)\C\2=C/c3[nH]c(c(c3C)C(=O)NCCN4CCCC4)C |
| Safety Data | Back Directory | [WGK Germany ]
WGK 3 | [Storage Class]
11 - Combustible Solids | [Hazard Classifications]
Eye Irrit. 2
Skin Irrit. 2 |
| Hazard Information | Back Directory | [Uses]
Labelled Toceranib, a multitargeted indolinone receptor tyrosine kinase (RTK) inhibitor. Toceranib exhibited activity against a variety of spontaneous malignancies in canine such as mast cell tumors,
mixed mammary carcinomas, soft tissue sarcomas, and multiple myeloma. | [Uses]
Toceranib is a multitargeted indolinone receptor tyrosine kinase (RTK) inhibitor. Toceranib exhibited activity against a variety of spontaneous malignancies in canine such as mast cell tumors, mixed m
ammary carcinomas, soft tissue sarcomas, and multiple myeloma. | [Uses]
Toceranib is a multitargeted indolinone receptor tyrosine kinase (RTK) inhibitor. Toceranib exhibited activity against a variety of spontaneous malignancies in canine such as mast cell tumors, mixed mammary carcinomas, soft tissue sarcomas, and multiple myeloma. | [Biological Activity]
toceranib is an inhibitor which blocks various tyrosine kinases expressed on the cell surface. receptor tyrosine kinases (rtks) are excellent candidates for molecular targeted therapy, because they play key roles in controlling cell proliferation and survival and are frequently dysregulated in a variety of malignancies. | [Biochem/physiol Actions]
Toceranib (SU11654) is a protein tyrosine kinase inhibitor that selectively targets stem cell factor receptor c-kit, including all forms of mutant Kit, as well as PDGFR and VEGFR. Toceranib exhibited Ki values of 5 nM for PDGFR and 6 nM for VEGFR. Toceranib phosphate is approved for use in mast cell cancer in dogs. | [Synthesis]
General procedure: 5-((Z)-(5-fluoro-2-oxoindolidine-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (100 g) was dissolved in dimethylformamide (500 ml), and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (221 g), N-(2-aminoethyl)pyrrole (45.6 g) and triethylamine (93 ml). The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solid product was collected by vacuum filtration and washed with ethanol. The resulting solid was slurried in ethanol (500 ml) by stirring at 64 °C for 1 h and subsequently cooled to room temperature. The solid was again collected by vacuum filtration, washed with ethanol and dried under vacuum to afford (Z)-5-((5-fluoro-2-oxoindol-3-ylidene)methyl)-2,4-dimethyl-N-(2-(pyrrolidin-1-yl)ethyl)-1H-pyrrole-3-carboxamide (101.5 g, 77% yield). The product was characterized by 1H-NMR (dimethylsulfoxide-d6): δ 1.60 (m, 4H, 2xCH2), 2.40,2.44 (2xs, 6H, 2xCH3), 2.50 (m, 4H, 2xCH2), 2.57,3.35 (2xm, 4H, 2xCH2), 7.53,7.70,7.73,7.76 (4 xm. 4H, aromatic and vinyl), 10.88 (s, 1H, CONH), 13.67 (s, 1H, pyrrole NH). Mass spectral analysis showed m/z 396 [M + 1]. | [in vitro]
toceranib inhibited kit phosphorylation and cell proliferation in a dose-dependent manner in the treatment-na?ve, parental c2 line (ic50 < 10 nm). in addition, chronic toc exposure resulted in c-kit mrna and kit protein overexpression in the toc-resistant sublines [1]. | [in vivo]
fourteen dogs with advanced mast cell tumors (mcts) were enrolled in a prevoius study, among which 11 dogs were evaluable for kit target modulation. of these, eight mcts showed reduced levels of phosphorylated kit relative to total kit after treatment with toceranib, compared with pretreatment biopsies. all four evaluable mcts expressing itd mutant c-kit showed modulation of kit phosphorylation, as did four of seven tumors expressing non-itd c-kit. [2]. | [IC 50]
PDGFRβ: 5 nM (Ki); Flk-1: 6 nM (Ki) | [storage]
Store at -20°C | [References]
[1] halsey ch, gustafson dl, rose bj, wolf-ringwall a, burnett rc, duval dl, avery ac, thamm dh. development of an in vitro model of acquired resistance to toceranib phosphate (palladia?) in canine mast cell tumor. bmc vet res. 2014;10:105. doi: 10.1186/1746-6148-10-105.
[2] pryer nk, lee lb, zadovaskaya r, yu x, sukbuntherng j, cherrington jm, london ca. proof of target for su11654: inhibition of kit phosphorylation in canine mast cell tumors. clin cancer res. 2003;9(15):5729-34. |
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| Company Name: |
J & K SCIENTIFIC LTD.
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| Telephone: |
18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
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