Onatasertib (CC 223)

Catalog No.S7886 Batch:S788601

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Technical Data

Formula

C21H27N5O3
Molecular Weight 397.47 CAS No. 1228013-30-6
Solubility (25°C)* In vitro DMSO 79 mg/mL (198.75 mM)
Ethanol 79 mg/mL (198.75 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Onatasertib (CC 223) is a potent, selective, and orally bioavailable mTOR inhibitor with IC50 of 16 nM, >200-fold selectivity over the related PI3K-α. Phase 1/2.
Targets
mTOR [1]
(Cell-free assay)		 cFMS [1]
(Cell-free assay)		 FLT4 [1]
(Cell-free assay)		 DNA-PK [1]
(Cell-free assay)
16 nM 28 nM 651 nM 840 nM
In vitro In a panel of cell lines, CC-223 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. [1]
In vivo In PC-3 tumor-bearing mice, CC-223 (25 mg/kg, p.o.) inhibits both mTORC1 and mTORC2. CC-223 (25 mg/kg, p.o.) also results in tumor growth inhibition by 47% to 95% in xenograft models of prostate, glioma, breast, lung, and colon. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Kinase assays mTOR.

    Reagents are prepared as follows:”Simple Tor buffer”: 10mM Tris pH 7.4, 100mM NaCl, 0.1% Tween-20, 1mM DTT. 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. The reaction is allowed to run for 60 minutes. The assay is stopped by adding 5 μL of 60 mM EDTA. Ten (10) μL of detection reagent mix is then added, and the mixture is allowed to sit at least 2 hours before reading on a Perkin Elmer Envision microplate reader set to detect Europium-based TR-FRET.
Cell Assay:[1]
  • Cell lines

    PC-3, CAL-51, A549,T47D,NCI-H460, HepG2, AU565, Hep3B, HCC, U87MG, HCT116, MDA-MB-231, and NCI-H23 cells

  • Concentrations

    ~ 10 μM

  • Incubation Time

    72 h

  • Method

    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.
Animal Study:[1]
  • Animal Models

    Mice bearing PC-3, U-87 MG, HCT 116, MDA-MB-231, or A549 tumors

  • Dosages

    25 mg/kg

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , PLoS One, 2017, 12(3):e0173252. ]

Selleck's Onatasertib (CC 223) has been cited by 2 publications

CC-223 inhibits human head and neck squamous cell carcinoma cell growth [Wang JY Biochem Biophys Res Commun, 2018, 496(4):1191-1196] PubMed: 29402408
CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo [Xie Z PLoS One, 2017, 12(3):e0173252] PubMed: 28334043

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.