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Onatasertib(CC-223)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Onatasertib(CC-223)图片
CAS NO:1228013-30-6
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)397.47
FormulaC21H27N5O3
CAS No.1228013-30-6
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 79 mg/mL (198.75 mM)
Water: <1 mg/mL
Ethanol: 79 mg/mL (198.75 mM)
SMILES OC(C)(C)C(N=C1)=CC=C1C(N=C2N3[C@@H]4CC[C@H](CC4)OC)=CN=C2NCC3=O
Synonyms CC223; Onatasertib; CC 223; CC-223
实验参考方法
In Vitro

In vitro activity: In a panel of cell lines, CC-223/Onatasertib inhibits both mTORC1 (S6RP and 4EBP1) and mTORC2 [AKT(S473)] markers with IC50 ranges of 27 to 184 nM for pS6RP, 120 to 1,050 nM for p4EBP1 and 11 to 150 nM for pAKT(S473), respectively. CC-223 also inhibits cell growth and induces apoptosis across a number of cancer cell lines.


Kinase Assay: Recombinant mTOR is diluted in this buffer to an assay concentration of 0.200ug/mL. ATP/Substrate solution: 0.075 mM ATP, 12.5 mM MnCl2, 50 mM Hepes, pH 7.4, 50mM β-GOP, 250 nM Microcystin LR, 0.25 mM EDTA, 5 mM DTT, and 3.5 μg/mL GST-p70S6. Dilution Curve: A 10-point, 1:3 dilution of compounds are prepared in neat DMSO at 50 times the final assay concentration. Detection reagent mix: 50 mM HEPES, pH 7.4 0.01% Triton X-100, 0.01% BSA, 0.1 mM EDTA, 12.7 ug/mL Cy5-anti-GST antibody, 9 ng/ml anti-phospho p70S6 antibody (Thr389), 627ng/mL anti-mouse IgG labeled with Lance Eu. To 20 uL of the Simple Tor buffer is added 0.5 uL of the compound Dilution Curve in DMSO. The final concentration range for compound is 30 to 0.0015 μM. To initiate the reaction, 5 μL of the ATP/substrate solution is added to the above.


Cell Assay: Compound is spotted via an acoustic dispenser (EDC ATS-100) into an empty 384-well plate. Cells are diluted to desired densities and added directly to the compound-spotted plates. Cells are allowed to grow for 72 hours. Viability is assessed via Cell Titer-Glo. All data are normalized and represented as a percentage of the DMSO-treated cells. Results are then expressed as GI50 and/or IC50 values.

In Vivo The antitumor activity of CC-223 in the PC-3 xenograft model is determined using a number of dosing paradigms. CC-223 significantly inhibits PC-3 tumor growth in a dose- and schedule-dependent manner. Dosing at 10 or 25 mg/kg, once daily, results in 46% (P<0.001) and 87% (P<0.001) reduction in tumor volume, respectively. Similar dose dependency is observed with twice-daily dosing at 5 or 10 mg/kg, corresponding to 65% (P<0.001) and 80% (P<0.001) tumor volume reductions. All dose levels are tolerated in the once-daily and twice-daily dosing studies, with only the 25 mg/kg/d group showing any significant body weight loss. These mice lost approximately 10% of their initial body weight after 3 weeks of dosing.
Animal model Mice bearing PC-3, U-87 MG, HCT 116, MDA-MB-231, or A549 tumors
Formulation & DosageSuspended in aqueous 0.5% carboxymethyl cellulose and 0.25% Tween-80.25 mg/kg.p.o.
References

Mol Cancer Ther. 2015 Jun;14(6):1295-305.