Sotrastaurin

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Chemical Structure| 425637-18-9 同义名 : AEB071
CAS号 : 425637-18-9
货号 : A517820
分子式 : C25H22N6O2
纯度 : 99%+
分子量 : 438.481
MDL号 : MFCD16038049
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(114.03 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：

2% DMSO+30% PEG 300+water 10 mg/mL

生物活性
靶点

  • PKCη

    PKCη, Ki:1.8 nM

  • PKCβ

    PKCβ1, Ki:0.64 nM

  • PKCε

    PKCε, Ki:3.2 nM

  • PKCθ

    PKCθ, Ki:0.22 nM
描述 Protein kinase C (PKC) is a serine/threonine protein kinase, which plays a crucial role in signaling transduction mechanisms in many cell types and tissues. Sotrastaurin (AEB071), as an immuno- suppressor, is a pan selective PKC inhibitor with Ki value of 0.95 nM, 0.64 nM, 2.1 nM, 3.2 nM, 1.8 nM and 0.22 nM for PKCα, PKCβ1, PKCδ, PKCε, PKCη and PKCθ (measured by scintillation proximity assay technology). Sotrastaurin suppresses T-cell activation, in a complementary and different manner to calcineurin inhibitor such as cyclosporine A. Sotrastaurin can effectively abrogate CD3/CD28 antibody and alloantigen-driven T-cell responses. Treatment with sotrastaurin at a concentration of 250 nM can markedly decrease proliferation responses induced by antibody- or phorbol ester treatment in mouse CD3 T cells. Both IL-2 and IFNγ levels were strongly inhibited by sotrastaurin (<1000 nM) in the transgenic TCR DO11.10 mouse CD4+ T cells after physiological stimulation with the antigenic OVA peptide. This inhibition on T cells may due to the suppression on the canonical NF-κB and NFAT transactivation pathway. Sotrastaurin strongly inhibited phorbol ester-induced adhesion responses of Jurkat cells with an IC50 value of 300 nM, in stark contrast with CsA treatment inactive up to 1 μM in this assay[1]. The almost completed inhibition of Sotrastaurin on CD25 expression was achieved at 2h, with >60% inhibition remaining 6h after administration in the T lymphocytes activated by anti-CD28 antibody in combination with PMA, from Lewis rats treated with a single oral dose of sotrastaurin on 30 mg/kg[2]. Oral administration of sotrastaurin on 30 mg/kg, b.i.d, showed immunosuppressive effect and led to pronounced prolongation survival in rats with heart allograft[2]. Sotrastaurin is being developed as an immunosuppressive for organ transplantation. Up to now, several phase 2 studies on efficacy, safety and tolerability of sotrastaurin on transplantation have been completed (see https://clinicaltrials.gov/).
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
92.1 0.5 μM Growth Inhibition Assay 3 h enhances IR-induced reduction in cell viability 24595385
92.1 0.5 μM Growth Inhibition Assay 3 h increases IR-induced cell cycle arrest  24595385
92.1 0-5 μM Growth Inhibition Assay 72 h inhibits cell growth dose dependently 22653968
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.28mL

0.46mL

0.23mL

11.40mL

2.28mL

1.14mL

22.81mL

4.56mL

2.28mL
参考文献

[1]Evenou JP, Wagner J, et al. The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation. J Pharmacol Exp Ther. 2009 Sep;330(3):792-801.

[2]Weckbecker G, Pally C, et al. Effects of the novel protein kinase C inhibitor AEB071 (Sotrastaurin) on rat cardiac allograft survival using single agent treatment or combination therapy with cyclosporine, everolimus or FTY720. Transpl Int. 2010 May 1;23(5):543-52.

[3]Naylor TL, Tang H, et al. Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas. Cancer Res. 2011 Apr 1;71(7):2643-53.