Home PI3K/Akt/mTOR mTOR inhibitor Onatasertib (CC 223)

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Onatasertib (CC 223) mTOR inhibitor

Cat.No.S7886

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) mTOR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 397.47

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Quality Control

Batch: S788601 DMSO]79 mg/mL]false]Ethanol]79 mg/mL]false]Water]Insoluble]false Purity: 99.57%
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99.57

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human PC3 cells Function assay 1 h Inhibition of mTORC2 in human PC3 cells assessed as inhibition of Akt phosphorylation at S473 after 1 hr, IC50=0.01 μM
human PC3 cells Function assay 1 h Inhibition of mTORC1 in human PC3 cells assessed as inhibition of S6 phosphorylation after 1 hr
human PC3 cells Function assay 1 h Inhibition of mTORC1 in human PC3 cells assessed as inhibition of S6 phosphorylation after 1 hr
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Chemical Information, Storage & Stability

Molecular Weight 397.47 Formula

C21H27N5O3

 Storage (From the date of receipt)
CAS No. 1228013-30-6 Download SDF Storage of Stock Solutions

Synonyms ATG-008 Smiles CC(C)(C1=NC=C(C=C1)C2=CN=C3C(=N2)N(C(=O)CN3)C4CCC(CC4)OC)O

Solubility

In vitro
Batch:

DMSO : 79 mg/mL (198.75 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 79 mg/mL

Water : Insoluble

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Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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Mechanism of Action

Targets/IC50/Ki
mTOR
(Cell-free assay)
16 nM
cFMS
(Cell-free assay)
28 nM
FLT4
(Cell-free assay)
651 nM
DNA-PK
(Cell-free assay)
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.
Kinase Assay
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 labelled 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.
In vivo
In PC-3 tumour-bearing mice, CC-223 (25 mg/kg, p.o.) inhibits both mTORC1 and mTORC2. CC-223 (25 mg/kg, p.o.) also results in tumour growth inhibition by 47% to 95% in xenograft models of prostate, glioma, breast, lung, and colon.
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02031419 Terminated
Lymphoma Large B-Cell Diffuse
Celgene
 December 18 2013 Phase 1
NCT01545947 Completed
Carcinoma Non-Small-Cell Lung|Non-Small Cell Lung Cancer
Celgene
 May 1 2012 Phase 1
NCT01177397 Completed
Multiple Myeloma|Diffuse Large B-Cell Lymphoma|Glioblastoma Multiforme|Hepatocellular Carcinoma|Non-Small Cell Lung Cancer|Neuroendocrine Tumors of Non-Pancreatic Origin|Hormone Receptor-Positive Breast Cancer
Celgene
 July 20 2010 Phase 1|Phase 2

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