Home MAPK ERK inhibitor SCH772984 For research use only.

SCH772984

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.

SCH772984 Chemical Structure

SCH772984 Chemical Structure

CAS No. 942183-80-4

Purity & Quality Control

Products often used together with SCH772984

Adezmapimod (SB203580)

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SP600125

SCH772984 and SP600125 suppress the upregulated LAGE3-induced proliferation, migration, and invasion of Hep3B cells.

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MG132

SCH772984-induced downregulation of UHRF1 and DNMT1 proteins is not rescued by MG132 in HCT116 cells.

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Phenformin HCl

Phenformin enhances the antiproliferative activity of SCH772984 in Mewo, M308, and SK-Mel-113 cells.

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SCH772984 Related Products

Signaling Pathway

ERK Signaling Pathways

ERK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
2P-ERK2 Growth Inhibition Assay IC50=0.24 nM 25350931
A375 Function assay 2 hrs Inhibition of ERK2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-ERK2 level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.004 μM. 25977981
A375 Function assay Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated ERK2 levels, IC50 = 0.004 μM. 28376306
COLO205 Antiproliferative assay 4 days Antiproliferative activity against human COLO205 cells harboring BRAF V600E/D mutant measured after 4 days, IC50 = 0.016 μM. 30034615
A375 Function assay 2 hrs Inhibition of ERK1/2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-RSK level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.02 μM. 25977981
A375 Function assay 2 hrs Inhibition of ERK1/2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-RSK level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.02 μM. 25977981
A375 Function assay Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated RSK levels, IC50 = 0.02 μM. 28376306
HT-29 Antiproliferative assay 4 days Antiproliferative activity against human HT-29 cells harboring BRAF V600E/D mutant measured after 4 days, IC50 = 0.059 μM. 30034615
HT-29 Antiproliferative assay Antiproliferative activity against human HT-29 cells harboring BRAF/KRAS mutant, IC50 = 0.059 μM. 29748051
A375 Antiproliferative assay 72 hrs Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant after 72 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.07 μM. 25977981
HT-29 Apoptosis assay Induction of apoptosis in human HT-29 cells harboring BRAF/KRAS mutant by caspase activation assay, IC50 = 0.096 μM. 29748051
Click to View More Cell Line Experimental Data

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.
Features Does not directly inhibit MEK1, MEK2, BRAF, or CRAF enzyme activity.
Targets
ERK2 [1]
(Cell-free assay)		 ERK1 [1]
(Cell-free assay)
1 nM 4 nM
In vitro
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]
Kinase Assay 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 Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot cyclin B1 / cyclin D1 / p21 pRSK / pERK / pAKT / pMEK DUSP1 / DUSP4 / DUSP6 pCRAF(S338, S289, S296, S301) Aurora B / ETS1 / ETS2 26725216
Growth inhibition assay Cell viability 30118499
Immunofluorescence TOMM20 pERK1/2 30833752
In Vivo
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]
Animal Research Animal Models Nude mice
Dosages 12.5 mg/kg, 25 mg/kg, 50 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 587.67 Formula

C33H33N9O2
CAS No. 942183-80-4 SDF Download SCH772984 SDF
Smiles C1CN(CC1C(=O)NC2=CC3=C(C=C2)NN=C3C4=CC=NC=C4)CC(=O)N5CCN(CC5)C6=CC=C(C=C6)C7=NC=CC=N7
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 14 mg/mL ( (23.82 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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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Frequently Asked Questions

Question 1:
I would like to inhibit Erk1/2 by treating the mice with the inhibitor. by what kind of administration way and at what concentration could it be done?

Answer:
SCH772984 can be administrated by I.P. The dosages can be used as: 12.5 mg/kg, 25 mg/kg, 50 mg/kg. For more detail information please find the paper below: http://cancerdiscovery.aacrjournals.org/content/3/7/742.full

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