SC66

产品说明书

Print
Chemical Structure| 871361-88-5 同义名 : -
CAS号 : 871361-88-5
货号 : A225521
分子式 : C18H16N2O
纯度 : 99%+
分子量 : 276.332
MDL号 : MFCD05025493
存储条件：

Pure form Sealed in dry,2-8°C

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

DMSO: 25 mg/mL(90.47 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
描述 The PI3K/AKT/mTOR signaling pathway is involved in various cellular processes such as cell proliferation, migration, survival and angiogenesis. The phosphatidylinositol-3,4,5-triphosphate (PIP3) binding function of pleckstrin homology (PH) domain is essential for the activation of oncogenic Akt/PKB kinase[3]. SC66 is an allosteric Akt inhibitor that affects AKT/mTOR signaling by a decrease in AKT phosphorylation levels and in total protein levels[4]. After treatment with increasing concentrations of SC-66, activating PIK3CA (E545K, E542K) and inactivating PTEN (R233*) mutations were identified in human cervical cancer. SC-66 effectively inhibited AKT, mTOR and mTOR substrates in C33A cells. SC-66 inhibited glucose uptake via reduced delivery of Glut1 and Glut4 to the cell membrane. SC-66 (1 µg/ml-56%) treatment decreased cell viability through a non-apoptotic mechanism. Decreases in cell viability were enhanced when AKT inhibitors were combined with 2-DG. The scratch assay showed a substantial reduction in cell migration upon SC-66 treatment[5]. A mouse xenograft tumor model of Hep3B cells was used to demonstrate the effectiveness in vivo of SC66 on HCC. Treatment with 25 mg/Kg SC66 via i.p. injection twice a week significantly reduced tumor volume to 37%. SC66 inhibit HCC cell viability with IC50 values of approximately 0.85 and 0.75 μg/ml at 48 and 72 hours, respectively for HepG2, HA22T/VGH and PLC/PRF/5 cells[4].
作用机制 SC66 manifests a dual inhibitory activity that directly interferes with the PH domain binding to PIP3 and facilitates Akt ubiquitination[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.62mL

0.72mL

0.36mL

18.09mL

3.62mL

1.81mL

36.19mL

7.24mL

3.62mL
参考文献

[1]Cusimano A, Puleio R, et al. Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells. Oncotarget. 2015 Jan 30;6(3):1707-22.

[2]Jo H, Lo PK, et al. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6486-91.

[3]Jo H, Lo PK, Li Y, Loison F, Green S, Wang J, Silberstein LE, Ye K, Chen H, Luo HR. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6486-91.

[4]Cusimano A, Puleio R, D'Alessandro N, Loria GR, McCubrey JA, Montalto G, Cervello M. Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells. Oncotarget. 2015 Jan 30;6(3):1707-22.

[5]Rashmi R, DeSelm C, Helms C, Bowcock A, Rogers BE, Rader JL, Grigsby PW, Schwarz JK. AKT inhibitors promote cell death in cervical cancer through disruption of mTOR signaling and glucose uptake. PLoS One. 2014 Apr 4;9(4):e92948.