CC-223

Catalog No.S7886

CC-223 Chemical Structure

Molecular Weight(MW): 397.47

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.

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  • Fig 1. CC-223 is cytotoxic and anti-proliferative to cultured human HCC cells. Cultured HCC cell lines (HepG2, KYN-2 and Huh-7 lines), L02 normal hepatocytes as well as the primary human HCC cells ("HCC1/2/3" lines) were either left untreated ("C", same for all figures) or treated with designated concentration of CC-223 (10–1000 nM), cells were further cultivated in conditional medium for indicated time; Cell survival (A, B, C and E), and proliferation (D) were tested by listed assays. Data were expressed as mean ± SD (Same for all figures). n = 5 means five replicate wells (Same for Figs 1–4). * p <0.05 vs. "C".

    PLoS One, 2017, 12(3):e0173252. . CC-223 purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description 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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human PC3 cells MmXGSpVv[3Srb36gZZN{[Xl? MVOxJIg> Mk[5TY5pcWKrdHnvckBw\iCvVF;SR|IhcW5iaIXtZY4hWEN|IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhSWu2IIDoc5NxcG:{eXzheIlwdiCjdDDTOFc{KGGodHXyJFEhcHJuIFnDOVA:OC5yMTFOwG0> M{PTZVI3ODh|NEe4
human PC3 cells MmjUSpVv[3Srb36gZZN{[Xl? MlznNUBp MWrJcohq[mm2aX;uJI9nKG2WT2LDNUBqdiCqdX3hckBRSzNiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBUPiCyaH;zdIhwenmuYYTpc44h[W[2ZYKgNUBpeg>? MmfDNlYxQDN2N{i=
human PC3 cells NWLZ[2Z6TnWwY4Tpc44h[XO|YYm= NV\mbYRZOSCq NIjVc4dKdmirYnn0bY9vKG:oIH3UU3JEOSCrbjDoeY1idiCSQ{OgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCVNjDwbI9{eGixconsZZRqd25iYX\0[ZIhOSCqch?= MUGyOlA5OzR5OB?=

... Click to View More Cell Line Experimental Data

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

Kinase Assay:[1]
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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]
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  • 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.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Mice bearing PC-3, U-87 MG, HCT 116, MDA-MB-231, or A549 tumors
  • Formulation: Suspended in aqueous 0.5% carboxymethyl cellulose and 0.25% Tween-80
  • Dosages: 25 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 79 mg/mL (198.75 mM)
Ethanol 79 mg/mL (198.75 mM)
Water 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.

Chemical Information

Molecular Weight 397.47
Formula

C21H27N5O3

CAS No. 1228013-30-6
Storage powder
Synonyms N/A

Bio Calculators

Molarity Calculator

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Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02031419 Recruiting Lymphoma, Large B-Cell, Diffuse Celgene Corporation December 2013 Phase 1
NCT01896323 Completed Healthy Volunteers Celgene Corporation|Celgene July 2013 Phase 1
NCT01611467 Completed Safety and Pharmacokinetics in Healthy Volunteer Subjects Celgene Corporation June 2012 Phase 1
NCT01545947 Completed Carcinoma, Non-Small-Cell Lung|Non-Small Cell Lung Cancer Celgene Corporation May 2012 Phase 1
NCT01177397 Active, not recruiting 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 2010 Phase 1|Phase 2

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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID