Onatasertib (CC 223)

Catalog No.S7886 Synonyms: ATG-008

For research use only.

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.

Onatasertib (CC 223) Chemical Structure

CAS No. 1228013-30-6

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

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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.
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human PC3 cells NVfHcJNJTnWwY4Tpc44h[XO|YYm= M1;xWlEhcA>? MUfJcohq[mm2aX;uJI9nKG2WT2LDNkBqdiCqdX3hckBRSzNiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBCc3RicHjvd5Bpd3K7bHH0bY9vKGG2IGO0O|Mh[W[2ZYKgNUBpeixiSVO1NF0xNjBzIN88US=> NYrWSJpUOjZyOEO0O|g>
human PC3 cells NE\vUGFHfW6ldHnvckBie3OjeR?= MonKNUBp MlrqTY5pcWKrdHnvckBw\iCvVF;SR|EhcW5iaIXtZY4hWEN|IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhWzZicHjvd5Bpd3K7bHH0bY9vKGGodHXyJFEhcHJ? MkLiNlYxQDN2N{i=
human PC3 cells NHmxXJVHfW6ldHnvckBie3OjeR?= M3rGTVEhcA>? MmjRTY5pcWKrdHnvckBw\iCvVF;SR|EhcW5iaIXtZY4hWEN|IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhWzZicHjvd5Bpd3K7bHH0bY9vKGGodHXyJFEhcHJ? MWKyOlA5OzR5OB?=
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 Research:[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 Research:[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.

Solubility (25°C)

In vitro

DMSO 79 mg/mL
(198.75 mM)
Water Insoluble
Ethanol '79 mg/mL

Chemical Information

Molecular Weight 397.47


CAS No. 1228013-30-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)(C1=NC=C(C=C1)C2=CN=C3C(=N2)N(C(=O)CN3)C4CCC(CC4)OC)O

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02031419 Active not recruiting Drug: CC-122|Drug: CC-223|Drug: Rituximab|Drug: CC-292 Lymphoma Large B-Cell Diffuse Celgene December 18 2013 Phase 1
NCT01545947 Completed Drug: CC-223 erlotinib|Drug: CC-223 oral azacitidine Carcinoma Non-Small-Cell Lung|Non-Small Cell Lung Cancer Celgene May 1 2012 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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