SCH772984

Catalog No.S7101 Batch:S710106

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Technical Data

Formula

C33H33N9O2
Molecular Weight 587.67 CAS No. 942183-80-4
Solubility (25°C)* In vitro DMSO 6 mg/mL (10.2 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description SCH772984 is a novel, specific inhibitor of ERK1/2 with IC50 values of 4 nM and 1 nM in cell-free assay, respectively, And show robust efficacy in RAS- or BRAF-mutant cancer cells.
Targets
ERK2 [1]
(Cell-free assay)		 ERK1 [1]
(Cell-free assay)
1 nM 4 nM
In vitro SCH772984 is a novel, selective and ATP competitive inhibitor of ERK1/2. SCH772984 inhibits phosphorylation of the ERK substrate p90 ribosomal S6 kinase (T359/S363 phospho-RSK) in a dose-dependent manner. SCH772984 also inhibits phosphorylation of residues in the activation loop of ERK itself. SCH772984 demonstrates EC50 values <500 nM in approximately 88% and 49% of BRAF-mutant or RAS-mutant tumor lines, respectively. Importantly, SCH772984 effectively inhibited MAPK signaling and cell proliferation in tumor cells resistant to concurrent treatment with BRAF and MEK inhibitors. [1]
In vivo SCH772984 induces tumor regressions in xenograft models at tolerated doses. SCH772984 effectively inhibites MAPK signaling and cell proliferation in BRAF or MEK inhibitor resistant models. [1]
Features Does not directly inhibit MEK1, MEK2, BRAF, or CRAF enzyme activity.

Protocol (from reference)

Kinase Assay:

[1]
  • ERK2 IMAP enzymatic assay

    SCH772984 is tested in 8 point dilution curves in duplicate against purified ERK2 or ERK1. The enzyme is added to the reaction plate. and incubated with the compound before adding a solution of substrate peptide and ATP. 14μl of diluted enzyme (0.3ng active ERK2 per reaction) is added to each well of a 384-well plate. The plates are gently shaken to mix the reagents and incubated for 45 minutes at room temperature. The reaction is stopped with 60μl of IMAP Binding Solution (1:2200 dilutions of IMAP beads in 1X Binding Buffer). The plates are incubated at room temperature for an additional 0.5 hours to allow complete binding of phosphopeptides to the IMAP beads. Plates are read on the LJL Analyst.
Cell Assay:

[1]
  • Cell lines

    BRAF-mutant or RAS-mutant tumor lines

  • Concentrations

    ~10 μM

  • Incubation Time

    5 days

  • Method

    Cell proliferation experiments are performed in a 96-well format (six replicates), and cells are plated at 4,000/well density. At 24 h after cell seeding, cells are treated with DMSO or 9 point IC50 dilution (0.001-10 μM) at 1% DMSO final for all concentrations. Viability is assayed on 5 days after dosing using ViaLight luminescence kit following the manufacturer’s recommendations. For cell line panel viability assay, cells are treated with SCH772984 for 4 days and assayed by CellTiterGlo luminescent cell viability assay.
Animal Study:

[1]
  • Animal Models

    Nude mice

  • Dosages

    12.5 mg/kg, 25 mg/kg, 50 mg/kg

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by Leuk Lymphoma, 2014, 1, 8]

, , Biochem Biophys Res Commun, 2017, 485(4):775-781

Data from [Data independently produced by , , Nature, 2016, 534(7609):647-51]

Data from [Data independently produced by , , Cell Research, 2015, 25: 561-573]

Selleck's SCH772984 has been cited by 643 publications

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer [ Nature, 2024, 629(8013):927-936] PubMed: 38588697
The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 [ Nat Commun, 2024, 15(1):383] PubMed: 38195627
SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers [ Nat Commun, 2024, 15(1):8002] PubMed: 39266533
Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis [ Nat Commun, 2024, 15(1):4108] PubMed: 38750011
Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis [ Nat Commun, 2024, 15(1):4108] PubMed: 38750011
Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death [ Nat Commun, 2024, 15(1):7037] PubMed: 39147750
Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes [ Acta Pharm Sin B, 2024, 14(4):1693-1710] PubMed: 38572108
PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer [ Cell Rep Med, 2024, 5(2):101420] PubMed: 38382468
The DNA-dependent protein kinase catalytic subunit exacerbates endotoxemia-induced myocardial microvascular injury by disrupting the MOTS-c/JNK pathway and inducing profilin-mediated lamellipodia degradation [ Theranostics, 2024, 14(4):1561-1582] PubMed: 38389837
LILRB1-HLA-G axis defines a checkpoint driving natural killer cell exhaustion in tuberculosis [ EMBO Mol Med, 2024, 10.1038/s44321-024-00106-1] PubMed: 39030302

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.