SC 66

Allosteric Akt inhibitor CAS# 871361-88-5

SC 66

Catalog No. BCC6160----Order now to get a substantial discount!

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SC 66: 5mg $58 In Stock
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Quality Control of SC 66

Number of papers citing our products

Chemical structure

SC 66

3D structure

Chemical Properties of SC 66

Cas No. 871361-88-5 SDF Download SDF
PubChem ID 6018993 Appearance Powder
Formula C18H16N2O M.Wt 276.33
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : 25 mg/mL (90.47 mM; Need ultrasonic)
Chemical Name (2E,6E)-2,6-bis(pyridin-4-ylmethylidene)cyclohexan-1-one
SMILES C1CC(=CC2=CC=NC=C2)C(=O)C(=CC3=CC=NC=C3)C1
Standard InChIKey CYVVJSKZRBZHAV-UNZYHPAISA-N
Standard InChI InChI=1S/C18H16N2O/c21-18-16(12-14-4-8-19-9-5-14)2-1-3-17(18)13-15-6-10-20-11-7-15/h4-13H,1-3H2/b16-12+,17-13+
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of SC 66

DescriptionAllosteric inhibitor of Akt; interferes with pleckstrin homology domain binding to PIP3 and facilitates Akt ubiquitination. Exhibits anticancer activity in vitro and in vivo.

SC 66 Dilution Calculator

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SC 66 Molarity Calculator

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Preparing Stock Solutions of SC 66

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.6189 mL 18.0943 mL 36.1886 mL 72.3772 mL 90.4715 mL
5 mM 0.7238 mL 3.6189 mL 7.2377 mL 14.4754 mL 18.0943 mL
10 mM 0.3619 mL 1.8094 mL 3.6189 mL 7.2377 mL 9.0472 mL
50 mM 0.0724 mL 0.3619 mL 0.7238 mL 1.4475 mL 1.8094 mL
100 mM 0.0362 mL 0.1809 mL 0.3619 mL 0.7238 mL 0.9047 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on SC 66

SC66 is a novel Akt inhibitor, reduces cell viability in a dose- and time-dependent manner, inhibits colony formation and induces apoptosis in hepatocellular carcinoma (HCC) cells.

In Vitro:SC66 inhibits cell viability and colony forming capacity of HCC cells with IC50s of 0.77,0.47,0.92,0.75 and 2.85 μg/mL at 72 hours for HepG2, Hep3B, PLC/PRF/5,HA22T/VGH and Huh7 cells. HepG2, HA22T/VGH and PLC/PRF/5 cells have similar IC50s of approximately 0.85 and 0.75 μg/mL at 48 and 72 hours, respectively. To determine whether the decrease in cell viability is related to apoptosis induction, TUNEL assays are performed in Hep3B and Huh7 cells treated with 1, 2 and 4 μg/mL of SC66 for 24 hours. In Hep3B cells the number of TUNEL-positive cells increased with increasing concentrations of SC66, whereas in Huh7 cells very few light brown-colored cells are observed only after treatment with 4 μg/mL SC66[1].

In Vivo:To demonstrate the effectiveness in vivo of SC66 on HCC, a mouse xenograft tumor model of Hep3B cells is used. When tumors became palpable, at a size of about 150 mm3, mice are randomized into three groups of 6 animals each. The treated group receive SC66 at 15 and 25 mg/kg twice a week via i.p. injection, while the untreated group receive the vehicle alone. Treatment with 25 mg/Kg SC66 significantly reduces tumor volume to 37% on day 17 when compared with tumors of the untreated group[1].

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

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References on SC 66

Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination.[Pubmed:21464312]

Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6486-91.

The phosphatidylinositol-3,4,5-triphosphate (PIP3) binding function of pleckstrin homology (PH) domain is essential for the activation of oncogenic Akt/PKB kinase. Following the PIP3-mediated activation at the membrane, the activated Akt is subjected to other regulatory events, including ubiquitination-mediated deactivation. Here, by identifying and characterizing an allosteric inhibitor, SC66, we show that the facilitated ubiquitination effectively terminates Akt signaling. Mechanistically, SC66 manifests a dual inhibitory activity that directly interferes with the PH domain binding to PIP3 and facilitates Akt ubiquitination. A known PH domain-dependent allosteric inhibitor, which stabilizes Akt, prevents the SC66-induced Akt ubiquitination. A cancer-relevant Akt1 (e17k) mutant is unstable, making it intrinsically sensitive to functional inhibition by SC66 in cellular contexts in which the PI3K inhibition has little inhibitory effect. As a result of its dual inhibitory activity, SC66 manifests a more effective growth suppression of transformed cells that contain a high level of Akt signaling, compared with other inhibitors of PIP3/Akt pathway. Finally, we show the anticancer activity of SC66 by using a soft agar assay as well as a mouse xenograft tumor model. In conclusion, in this study, we not only identify a dual-function Akt inhibitor, but also demonstrate that Akt ubiquitination could be chemically exploited to effectively facilitate its deactivation, thus identifying an avenue for pharmacological intervention in Akt signaling.

Description

SC66 is an Akt inhibitor, reduces cell viability in a dose- and time-dependent manner, inhibits colony formation and induces apoptosis in hepatocellular carcinoma (HCC) cells.

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