JavaScript seems to be disabled in your browser. For the best experience on our site, be sure to turn on Javascript in your browser.
Tel: +1-832-696-8203
Email: [email protected]
Worldwide Distributors
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AST487 is an inhibitor of RET kinase with IC50 value of 0.88μM [1].
AST487 belongs to the N,N’-diphenyl urea class. It inhibit the activity of RET kinase as well as many other kinases( such as KDR, Flt-3 and c-Kit) in vitro. In the cell assay, the inhibition effect of AST487 is displayed both in PC-RET/PTC3 cells and TT cells, which harbor an endogenous activating point mutation of RET (RETC634W). AST487 decreases RET autophosphorylation and activation of PLCγ and ERK with a dose-dependent manner. Additionally, AST487 is also found to inhibit the growth of human thyroid cancer cell lines with RET, but not BRAF mutations. It supports the selectivity of AST487 for RET. In vivo assay shows that AST487 causes significant reductions in the size of NIH3T3-RETC634W xenografts with doses >30 mg/kg/d and oral administration of AST487 at 50 or 30 mg/kg/d decreases mean tumor volume in mice [1].
References:[1] Nagako Akeno-Stuart, Michelle Croyle, Jeffrey A. Knauf, et al. The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 2007, 67:6956-6964.
Cell lines
Baf3 cells
Preparation method
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions
10 min; IC50=34±4 nmol/L
Applications
Data derived from a panel of Baf3 murine pro–B cell lymphoma lines rendered growth factor–independent by transduction with various activated tyrosine kinases, suggested cellular specificity for RET-driven proliferation (IC50 for PTC3-RET–driven Baf3 cells, 34±4 nmol/L), with activity against FLT3 as well, and to a lesser extent,Bcr-ABL–dependent proliferation
Animal models
Female athymic nude mice
Dosage form
50 mg/kg; oral taken
NVP-AST487 given p.o. evoked a dose-dependent inhibition of growth of NIH3T3-RETC634W xenografts, with doses >30 mg/kg/d causing significant reductions in tumor size. The effects of the compound on RET expression and phosphorylation in tumor extracts was analyzed 6 h following the final treatment. Reductions in tumor RET phosphorylation in NVP-AST487–treated animals were clearly seen, particularly at doses ≥30 mg/kg. Interestingly, there was also a dose-dependent decrease of RET expression, with one of three tumors analyzed in the 30 mg/kg group and three of three tumors in the 50 mg/kg group showing a dramatic reduction in RET protein levels.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1] Yu K, Toral-Barza L, Shi C, et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin[J]. Cancer research, 2009, 69(15): 6232-6240.