Mubritinib

Names

[ Name ]:
Mubritinib

[Synonym ]:
Mubritinib (TAK 165)
UNII-V734AZP9BR
1-(4-{4-[(2-{(E)-2-[4-(Trifluoromethyl)phenyl]vinyl}-1,3-oxazol-4-yl)methoxy]phenyl}butyl)-1H-1,2,3-triazole
Mubritinib,TAK 165,TAK165
Oxazole, 4-[[4-[4-(1H-1,2,3-triazol-1-yl)butyl]phenoxy]methyl]-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-
(E)-1-(4-(4-((2-(4-(trifluoromethyl)styryl)oxazol-4-yl)methoxy)phenyl)butyl)-1H-1,2,3-triazole
TAK 165
Mubritinib
cc-594
1H-1,2,3-triazole, 1-(4-(4-((2-((1E)-2-(4-(trifluoromethyl)phenyl)ethenyl)-4-oxazolyl)methoxy)phenyl)butyl)-
S2216_Selleck

Biological Activity

[Description]:

Mubritinib (TAK-165) is a potent and selective EGFR2/HER2 inhibitor with an IC50 of 6 nM.

[Related Catalog]:

Research Areas >> Cancer

[Target]

HER2:6 nM (IC50)

[In Vitro]

TAK-165 specifically inhibits HER2 tyrosine kinase with an IC50 6 nM and does not inhibit other types tyrosine kinase up to 25 000 nM. TAK-165 inhibits HER2 phosphorylation and its down-stream Akt and MAPK in HER2 strongly expressing cells (BT474 breast cancer cell line). TAK-165 sensitivity depends on HER2 levels of each cell line. Especially, BT474 cells which over-express HER2 strongly is highly sensitive (IC50=0.005 µM) and PC-3 cells which express HER2 very weakly is less sensitive (IC50=4.62 µM). But, HT1376 and ACHN cells that over-expressed EGFR showed high IC50 (IC50>25 µM)[1].

[In Vivo]

In the xenograft model, treatment with TAK-165 significantly inhibits growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect after 14 days treatment are 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively[1].

[Cell Assay]

Cells are treated with TAK-165 at various concentrations for 72 h. After the incubation period, the cells are counted. The IC50 value is calculated from a dose–response curve generated by least-squares linear regression of the response[1].

[Animal admin]

Mice: UMUC-3 and LN-REC4 cells are implanted with 50% Matrigel solution. After the tumor volume reaches 200–300 mm3 in LN-REC4 and UMUC-3 cells and to 100–200 mm3 in ACHN, the mice are treated orally twice daily for 14 days with vehicle (control) or 10 or 20 mg/kg per day of TAK-165. In the Herceptin study against UMUC-3, treatments consist of a twice weekly intraperitoneal injection of 20 mg/kg Herceptin in PBS for 2 weeks. Tumor growth is assessed by electronic caliper measurement of tumor diameter in two dimensions, and tumor volume is calculated[1].

[References]

[1]. Nagasawa J, et al. Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo. Int J Urol. 2006 May;13(5):587-92.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
620.9±65.0 °C at 760 mmHg

[ Melting Point ]:
158.0 to 162.0 °C

[ Molecular Formula ]:
C₂₅H₂₃F₃N₄O₂

[ Molecular Weight ]:
468.471

[ Flash Point ]:
329.3±34.3 °C

[ Exact Mass ]:
468.177307

[ PSA ]:
65.97000

[ LogP ]:
5.91

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.578

[ Storage condition ]:
Store at +4°C

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Related Compounds

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