Home MAPK ERK inhibitor CC-90003

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CC-90003 ERK inhibitor

Cat.No.S8801

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 ERK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 458.44

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Quality Control

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

Chemical Information, Storage & Stability

Molecular Weight 458.44 Formula

C22H21F3N6O2

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 1621999-82-3 -- Storage of Stock Solutions

Synonyms N/A Smiles CC1=CC(=C(C=C1)NC2=NC(=NC=C2C(F)(F)F)NC3=CC(=NC=C3C)OC)NC(=O)C=C

Solubility

In vitro
Batch:

DMSO : 92 mg/mL (200.68 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
ERK1 [1]
ERK2 [1]
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 this compound 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 this chemical. 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 this compound. In many, but not all cases, it had cytotoxic effects in KRAS-mutant PDAC, lung cancer, and colorectal cancer cell lines. It does not significantly inhibit proliferation of normal lung fibroblasts or bronchial epithelial cells[1].
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. This compound inhibits tumor growth in vivo of three KRAS-mutant PDX models[1].
References

Clinical Trial Information

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

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02313012 Terminated
Neoplasm Metastasis
Celgene
 January 5 2015 Phase 1

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