Reagents and instruments for immunology, cell biology and molecular biology.

SCH772984 [942183-80-4]

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Cat# HY-50846-1ml

Size : 10mM/1mL

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Phone : +1 850 650 7790

Brand : MedChemExpress

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Phone : +1 850 650 7790

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	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.

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 BRAF^V600E 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).

Molecular Weight

587.67

Formula

C₃₃H₃₃N₉O₂

CAS No.

942183-80-4

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Solvent & Solubility

In Vitro:

DMSO : 30 mg/mL (51.05 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
10 mM	0.1702 mL	0.8508 mL	1.7016 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: ≥ 3 mg/mL (5.10 mM); Clear solution

This protocol yields a clear solution of ≥ 3 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (30.0 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: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: ≥ 2.4 mg/mL (4.08 mM); Clear solution
Protocol 3

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 1.43 mg/mL (2.43 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 1.43 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 (14.3 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.
Protocol 4

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 1.43 mg/mL (2.43 mM); Clear solution

This protocol yields a clear solution of ≥ 1.43 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (14.3 mg/mL) to 900 μL Corn oil, and mix evenly.

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: 20% SBE-β-CD in Saline adjusted to pH 4-4.5 with 1 N Acetic
Solubility: 20 mg/mL (34.03 mM); Clear solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 50% PEG300 50% PBS
Solubility: 10 mg/mL (17.02 mM); Suspended solution; Need ultrasonic

Purity & Documentation

Purity: 99.83%

Data Sheet (277 KB) SDS (393 KB)

COA (247 KB) HNMR (300 KB) RP-HPLC (220 KB) LCMS (98 KB)

Handling Instructions (2659 KB)

References

[1]. Morris EJ, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-50. [Content Brief]

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SCH772984 [942183-80-4]

Cat# HY-50846-1ml

Contact local distributor :

Brand : MedChemExpress

Contact local distributor :

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