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AST 487

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Chemical Structure| 630124-46-8 同义名 : NVP-AST 487
CAS号 : 630124-46-8
货号 : A248926
分子式 : C26H30F3N7O2
纯度 : 99%+
分子量 : 529.557
MDL号 : MFCD11983171
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(198.28 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The RET kinase has emerged as a promising target for the therapy of medullary thyroid cancers (MTC) and of a subset of papillary thyroid cancers[3]. AST-487, a N, N′-diphenyl urea with an IC50 of 0.88 μM on RET kinase, inhibited RET autophosphorylation and activation of downstream effectors, and potently inhibited the growth of human thyroid cancer cell lines with activating mutations of RET but not of lines without RET mutations. AST-487 induced a dose-dependent growth inhibition of xenografts of NIH3T3 cells expressing oncogenic RET, and of the MTC cell line TT in nude mice. Additionally, AST-487 inhibited calcitonin gene expression in vitro in TT cells, in part, through decreased gene transcription[3]. After a single oral administration of 15 mg/kg of AST-487 to OF1 mice, a mean peak plasma level (Cmax) of 0.505±0.078 μM SE is achieved after 0.5 h. Similar levels of AST 487 are found in the plasma of mice up to 6 h after oral administration, with a Clast of 21±4 nM at 24 h[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.89mL

0.38mL

0.19mL

9.44mL

1.89mL

0.94mL

18.88mL

3.78mL

1.89mL
参考文献

[1]Weisberg E, Roesel J, et al. Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells. Blood. 2008 Dec 15;112(13):5161-70.

[2]Akeno-Stuart N, Croyle M, 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 Jul 15;67(14):6956-64.

[3]Akeno-Stuart N, Croyle M, Knauf JA, Malaguarnera R, Vitagliano D, Santoro M, Stephan C, Grosios K, Wartmann M, Cozens R, Caravatti G, Fabbro D, Lane HA, Fagin JA. The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 2007 Jul 15;67(14):6956-64. doi: 10.1158/0008-5472.CAN-06-4605. PMID: 17638907.