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> SCH772984 [942183-80-4]

SCH772984 [942183-80-4]

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Référence HY-50846-10mg

Conditionnement : 10mg

Marque : MedChemExpress


Description

SCH772984 is a highly selective and ATP-competitive ERK inhibitor, with IC50s of 4 and 1 nM for ERK1 and ERK2, respectively. SCH772984 has antitumor activity in MAPK inhibitor-na?ve and MAPK inhibitor-resistant cells containing BRAF or RAS mutations[1].

IC50 & Target[1]

ERK2

1 nM (IC50)

ERK1

4 nM (IC50)

Cellular Effect
Cell Line Type Value Description References
A-375 IC50
0.004 μM
Compound: SCH772984
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
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
[PMID: 25977981]
A-375 IC50
0.02 μM
Compound: SCH772984
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
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
[PMID: 25977981]
A-375 IC50
0.07 μM
Compound: SCH772984
Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant after 72 hrs by Cellomics ArrayScanTM VTI imaging analysis
Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant after 72 hrs by Cellomics ArrayScanTM VTI imaging analysis
[PMID: 25977981]
A375-SM IC50
39 nM
Compound: 1; SCH772984
Antiproliferative activity against human A375SM cells harboring BRAF V600E mutant measured after 96 hrs by Cell Titer-Glo assay
Antiproliferative activity against human A375SM cells harboring BRAF V600E mutant measured after 96 hrs by Cell Titer-Glo assay
[PMID: 27329786]
COLO 205 IC50
16 nM
Compound: 5; SCH772984
Antiproliferative activity against human COLO205 cells harboring BRAF V600E/D mutant measured after 4 days
Antiproliferative activity against human COLO205 cells harboring BRAF V600E/D mutant measured after 4 days
[PMID: 30034615]
HeLa IC50
>50 μM
Compound: 3; SCH772984
Antiproliferative activity against human HeLa cells assessed as reduction in cell viability measured after 24 hrs
Antiproliferative activity against human HeLa cells assessed as reduction in cell viability measured after 24 hrs
[PMID: 32078308]
HL-60 IC50
1.06 μM
Compound: 3; SCH772984
Antiproliferative activity against human HL60 cells assessed as reduction in cell viability measured after 24 hrs
Antiproliferative activity against human HL60 cells assessed as reduction in cell viability measured after 24 hrs
[PMID: 32078308]
HT-29 IC50
59 nM
Compound: 5; SCH772984
Antiproliferative activity against human HT-29 cells harboring BRAF V600E/D mutant measured after 4 days
Antiproliferative activity against human HT-29 cells harboring BRAF V600E/D mutant measured after 4 days
[PMID: 30034615]
HT-29 IC50
59 nM
Compound: 5; SCH772984
Antiproliferative activity against human HT-29 cells harboring BRAF/KRAS mutant
Antiproliferative activity against human HT-29 cells harboring BRAF/KRAS mutant
[PMID: 29748051]
HT-29 IC50
96 nM
Compound: 5; SCH772984
Induction of apoptosis in human HT-29 cells harboring BRAF/KRAS mutant by caspase activation assay
Induction of apoptosis in human HT-29 cells harboring BRAF/KRAS mutant by caspase activation assay
[PMID: 29748051]
MKN-74 IC50
>50 μM
Compound: 3; SCH772984
Antiproliferative activity against human MKN74 cells assessed as reduction in cell viability measured after 24 hrs
Antiproliferative activity against human MKN74 cells assessed as reduction in cell viability measured after 24 hrs
[PMID: 32078308]
In Vitro

SCH772984 (300 nM; 24-48hours) results in a G1 arrest in SCH772984-sensitive melanoma cells[1].
SCH772984 (3-300 nM; 24 hours) inhibits ERK and RSK phosphorylation[1].
SCH772984 shows EC50 values less than 500 nM in approximately 88% and 49% of BRAF-mutant (n=25) or RAS-mutant (n=35) tumor lines, respectively[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

SCH772984 Related Antibodies

Cell Cycle Analysis[1]

Cell Line: LOX cells (SCH772984-sensitive melanoma cells)
Concentration: 300 nM
Incubation Time: 24, 48 hours
Result: Revealed a G1 arrest as well as an increase in the sub-G1 fraction indicative of apoptosis.

Western Blot Analysis[1]

Cell Line: LOX BRAFV600E melanoma cells
Concentration: 3, 10, 30, 100, 300 nM
Incubation Time: 24 hours
Result: A dose-dependent inhibition of phosphorylation of the ERK substrate RSK (T359/S363 phospho-RSK), and also inhibited phosphorylation of residues in the activation loop of ERK itself (T202/Y204 and T185/Y187 of ERK1 and ERK2, respectively).
In Vivo

SCH772984 (12.5-50 mg/kg; i.p.; twice daily for 14 days) leads to 98% tumor regression[1].
Dose-dependent antitumor activity is also observed in the KRAS-mutant pancreatic MiaPaCa model, with 36% regression at 50 mg/kg twice daily. Importantly, tumor regression is accompanied by robust inhibition of ERK phosphorylation in tumor tissue. SCH772984 is well tolerated on this schedule as measured by morbidity, lethality, or body weight loss[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Female nude mice bearing human LOX BRAFV600E tumors[1]
Dosage: 12.5, 25, 50 mg/kg
Administration: Intraperitoneal injection; twice daily for 14 days
Result: Tumor regressions were observed at all doses, such as 17% at 12.5 mg/kg, 84% at 25 mg/kg, and 98% at 50 mg/kg).
Masse moléculaire

587.67

Formule

C33H33N9O2
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C([C@H](CC1)CN1CC(N(CC2)CCN2C(C=C3)=CC=C3C4=NC=CC=N4)=O)NC5=CC6=C(C=C5)NN=C6C7=CC=NC=C7
Livraison

Room temperature in continental US; may vary elsewhere.
Stockage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 1 year
-20°C 6 months
Solvant et solubilité
In Vitro: 

DMSO : 5 mg/mL (8.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.7016 mL 8.5082 mL 17.0164 mL
5 mM 0.3403 mL 1.7016 mL 3.4033 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: 0.5 mg/mL (0.85 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 0.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 0.5 mg/mL (0.85 mM); Clear solution

    This protocol yields a clear solution of ≥ 0.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  50% PEG300    50% PBS

    Solubility: 10 mg/mL (17.02 mM); Suspended solution; Need ultrasonic
Pureté et documentation
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