Home MAPK ERK inhibitor CC-90003 For research use only.

CC-90003

CC-90003 is an irreversible inhibitor of ERK1/2 with IC50s in the 10-20 nM range and shows good kinase selectivity in a 258-kinase biochemical assay.

CC-90003 Chemical Structure

CC-90003 Chemical Structure

CAS No. 1621999-82-3

Purity & Quality Control

Batch: S880101 DMSO]92 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.69%
99.69

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Biological Activity

Description CC-90003 is an irreversible inhibitor of ERK1/2 with IC50s in the 10-20 nM range and shows good kinase selectivity in a 258-kinase biochemical assay.
Targets
ERK1 [1] ERK2 [1]
In vitro
In vitro

In biochemical, cellular, and mass spectrometry assays of 347 kinases, CC-90003 was found to strongly inhibit kinase activities of ERK1 and ERK2 with IC50s in the 10 to 20 nmol/L range and had good kinase selectivity. In a 258-kinase biochemical assay panel, significant inhibition of 213 kinases (<50% inhibition), moderate inhibition of 28 kinases (50%–80% inhibition), and >80% inhibition of 17 kinases by CC-90003 were found. In an ActivX cellular kinase screening using A375 BRAF V600E-mutant melanoma cell line, only 5 of 194 kinases (ERK1, ERK2, MKK4, MKK6, and FAK) were inhibited by >80% at 1 mmol/L of CC-90003. At the same concentration, no significant inhibition (<14%) was found in a Cerep panel of 40 nonkinase enzymes and receptors. Through our iterative analyses, only 3 kinases, in addition to ERK1/2, were inhibited in cells at biologically relevant concentrations: KDR, FLT3, and PDGFRa. Tumors with BRAF mutations were particularly sensitive to CC-90003. In many, but not all cases, CC-90003 had cytotoxic effects in KRAS-mutant PDAC, lung cancer, and colorectal cancer cell lines. CC-90003 does not significantly inhibit proliferation of normal lung fibroblasts or bronchial epithelial cells[1].
Cell Research Cell lines KRAS-mutant cell lines
Concentrations --
Incubation Time 72 h
Method

The cells were plated at a density of 3,000 cells/well in 90 mL of growth media on 96-well clear bottom black-well plates and incubated with overnight under standard cell culture growth conditions at 37 C with 5% CO2. The followinging day, one plate for each cell line was used for "Day 0" cell growth control readout, whereas others were treated with 9-point3-fold dilutions of one compound or combination of compounds, and a DMSO control. Each concentration was tested in triplicate. Cell viability was measured 72 hours later.
In Vivo
In vivo

In in vivo studies of an HCT-116 xenograft model, CC-90003 was well tolerated at a range of doses (12.5 mg b.i.d.-100 mg qd), although doses of 50 mpk b.i.d. and 75 mpk b.i.d. group caused mortality by days 6 to 18 of study. Both dosing schedules (qd and b.i.d.) leads to tumor growth inhibition. CC-90003 inhibits tumor growth in vivo of three KRAS-mutant PDX models[1].
Animal Research Animal Models Female athymic nude mice inoculated subcutaneously with 5×106 HCT-116 cancer cells
Dosages 100 mg/kg qd and 50 mg/kg qd; 25 mg/kg b.i.d. and 12.5 mg/kg b.i.d.
Administration orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02313012 Terminated
Neoplasm Metastasis
Celgene
 January 5 2015 Phase 1

Chemical Information & Solubility

Molecular Weight 458.44 Formula

C22H21F3N6O2
CAS No. 1621999-82-3 SDF --
Smiles CC1=CC(=C(C=C1)NC2=NC(=NC=C2C(F)(F)F)NC3=CC(=NC=C3C)OC)NC(=O)C=C
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 92 mg/mL ( (200.68 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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

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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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