630124-46-8 Usage
Description
AST 487, also known as N-[4-[(4-Ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-N''-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea, is a small molecule inhibitor that targets multiple receptor tyrosine kinases (RTKs), including RET, FLT3, KDR, c-Abl, and c-Kit. It has demonstrated the ability to inhibit the autophosphorylation and activation of downstream effectors of these kinases, making it a promising candidate for the treatment of various cancers and other diseases.
Uses
Used in Oncology:
AST 487 is used as an anticancer agent for the treatment of human thyroid cancer cells with activating mutations of RET. It has been shown to inhibit RET autophosphorylation and activation of downstream effectors, preventing the growth of these cancer cells.
Additionally, AST 487 is used as an antiproliferative agent for primary cells from acute myelocytic leukemia patients and on cell lines expressing FLT3-ITD or FLT3 kinase domain point mutants. It demonstrates antiproliferative effects on these cells, making it a potential therapeutic option for the treatment of acute myelocytic leukemia.
Used in COVID-19 Research:
AST 487 is also used as a COVID-19-related research product. While its specific application in this context is not detailed in the provided materials, it may be utilized in the investigation of potential therapeutic effects against the SARS-CoV-2 virus or related biological processes.
Biological Activity
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.
Check Digit Verification of cas no
The CAS Registry Mumber 630124-46-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,3,0,1,2 and 4 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 630124-46:
(8*6)+(7*3)+(6*0)+(5*1)+(4*2)+(3*4)+(2*4)+(1*6)=108
108 % 10 = 8
So 630124-46-8 is a valid CAS Registry Number.
630124-46-8Relevant articles and documents
Syntheses of a triad of Flt3 kinase inhibitors: From bench to pilot plant
Shieh, Wen-Chung,Mckenna, Joe,Sclafani, Joseph A.,Xue, Song,Girgis, Michael,Vivelo, James,Radetich, Branko,Prasad, Kapa
, p. 1146 - 1155 (2013/01/03)
We have designed and developed an alternative synthesis for the manufacturing of a triad of Flt3 kinase inhibitors (AST487, ATH686, and AUZ454) to support clinical assessments of patients with Flt3-dependent tumor diseases. The new synthesis is convergent
