Splitomicin

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Chemical Structure| 5690-03-9 同义名 : Splitomycin;1-Naphthalenepropanoic Acid
CAS号 : 5690-03-9
货号 : A473757
分子式 : C13H10O2
纯度 : 99%
分子量 : 198.217
MDL号 : MFCD08705254
存储条件：

Pure form Inert atmosphere,2-8°C

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

DMSO: 105 mg/mL(529.72 mM)，配合低频超声助溶，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
靶点

  • HDAC

    Sir2p, IC50:60 μM
描述 Sirtuins 1-7 (SIRT1-7) belong to the third class of deacetylase enzymes, which are dependent on NAD(+) for activity. Sirtuins activity is linked to gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection, and healthy aging[3].Splitomicin (Splitomycin) is a selective Sir2p inhibitor. Splitomicin inhibits NAD+-dependent HDAC activity of Sir2 protein. Splitomicin induces dose-dependent inhibition of HDAC in the yeast extract with an IC50 of 60 μM[4].The Sirt1 inhibitor,Sirtinol induced senescence-like growth arrest characterized by induction of senescence-associated beta-galactosidase activity and increased expression of plasminogen activator inhibitor 1 in human breast cancer MCF-7 cells and lung cancer H1299 cells. Sirtinol-induced senescence-like growth arrest was accompanied by impaired activation of mitogen-activated protein kinase (MAPK) pathways, namely, extracellular-regulated protein kinase, c-jun N-terminal kinase and p38 MAPK, in response to epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). Active Ras was reduced in Sirtinol-treated senescent cells compared with untreated cells. However, tyrosine phosphorylation of the receptors for EGF and IGF-I and Akt/PKB activation were unaltered by Sirtinol treatment[5].Sirt1 inhibition by splitomicin or sirtinol enhanced cytokine-induced endothelial TF protein expression as well as surface activity, while TF pathway inhibitor protein expression did not change. Sirt1 inhibition further enhanced TF mRNA expression, TF promoter activity, and nuclear translocation as well as DNA binding of the p65 subunit of nuclear factor-kappa B (NFκB/p65). Sirt1 siRNA enhanced TF protein and mRNA expression, and this effect was reduced in NFκB/p65(-/-) mouse embryonic fibroblasts reconstituted with non-acetylatable Lys(310)-mutant NFκB/p65. Activation of the mitogen-activated protein kinases p38, c-Jun NH(2)-terminal kinase, and p44/42 (ERK) remained unaffected. In vivo, mice treated with the Sirt1 inhibitor splitomicin exhibited enhanced TF activity in the arterial vessel wall and accelerated carotid artery thrombus formation in a photochemical injury model[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

5.04mL

1.01mL

0.50mL

25.22mL

5.04mL

2.52mL

50.45mL

10.09mL

5.04mL
参考文献

[1]Liu FC, Liao CH, et al. Splitomicin suppresses human platelet aggregation via inhibition of cyclic AMP phosphodiesterase and intracellular Ca++ release. Thromb Res. 2009 Jun;124(2):199-207.

[2]Bedalov A, Gatbonton T, et al. Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15113-8.

[3] José M Villalba,et al. Sirtuin activators and inhibitors. Biofactors. Sep-Oct 2012;38(5):349-59.

[4] Bedalov A, et al. Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15113-8.

[5] Ota H, et al. Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene. 2006 Jan 12;25(2):176-85.

[6]Breitenstein A, et al. Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells. Cardiovasc Res. 2011 Feb 1;89(2):464-72.