Enzastaurin (LY317615) 是一种有效的

Enzastaurin  (Synonyms: 恩扎妥林; LY317615)

Enzastaurin (LY317615) 是一种有效的 PKCβ 抑制剂，IC₅₀ 值为 6 nM。Enzastaurin 对 PKCβ 选择性是 PKCα，PKCγ 和 PKCε 的 6-20 倍。

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生物活性    
Enzastaurin (LY317615) is a potent and selective PKCβ inhibitor with an IC50 of 6 nM, showing 6- to 20-fold selectivity over PKCα, PKCγ and PKCε[1].

体外研究(In Vitro)    
Enzastaurin (LY317615) application results in a marked dose-dependent inhibition of growth in all MM cell lines investigated, including MM.1S, MM.1R, RPMI 8226 (RPMI), RPMI-Dox40 (Dox40), NCI-H929, KMS-11, OPM-2, and U266, with IC50 from 0.6-1.6 μM. Enzastaurin direct impacts human tumor cells, inducing apoptosis and suppressing proliferation in cultured tumor cells. Enzastaurin also suppresses the phosphorylation of GSK3βser9, ribosomal protein S6S240/244, and AKTThr308 while having no direct effect on VEGFR phosphorylation[1].
Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. When combined with GSK3 inhibitors, enzastaurin demonstrates an enhancement of cytotoxicity levels. Treatment with a combination of enzastaurin and the GSK3 inhibitor AR-A014418 leads to increased levels of β-catenin total protein and β-catenin-mediated transcription. Blocking of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin induces the same cytotoxic effects as that of enzastaurin plus AR-A014418. Additionally, treatment with enzastaurin and AR-A014418 decreases the mRNA levels and surface expression of CD44[2].

体内研究(In Vivo)    
Treatment of xenografts with Enzastaurin and radiation produces greater reductions in density of microvessels than either treatment alone. The decrease in microvessel density corresponds to delayed tumor growth[3].

分子量    
515.61

性状    
Solid

Formula    
C32H29N5O2

CAS 号    
170364-57-5

中文名称    
恩扎妥林

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 8.33 mg/mL (16.16 mM; Need ultrasonic)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    1.9395 mL    9.6973 mL    19.3945 mL
5 mM    0.3879 mL    1.9395 mL    3.8789 mL
10 mM    0.1939 mL    0.9697 mL    1.9395 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 0.83 mg/mL (1.61 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: 0.83 mg/mL (1.61 mM); Suspended solution; Need ultrasonic
 

参考文献

[1]. Graff JR, et al. The protein kinase Cbeta-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Res, 2005, 65(16),  [Content Brief] [2]. Rovedo MA, et al. Inhibition of glycogen synthase kinase-3 increases the cytotoxicity of enzastaurin. J Invest Dermatol, 2011, 131(7), 1442-1449.  [Content Brief] [3]. Podar K, et al. Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl). Blood, 2007, 109(4), 1669-1677.  [Content Brief]