SCH772984 |
Catalog No.GC16001
One-Click Copy Product Info
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SCH772984 is a novel, potent, ATP-competitive inhibitor of ERK1 and ERK2 with IC50 values of 4nM and 1nM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 942183-80-4
Sample solution is provided at 25 µL, 10mM.
SCH772984 is a novel, potent, ATP-competitive inhibitor of ERK1 and ERK2 with IC50 values of 4nM and 1nM, respectively[1]. SCH772984 inhibits phosphorylation of the ERK substrate p90 ribosomal S6 kinase (T359/S363 phospho-RSK) and also inhibits phosphorylation of residues in the activation loop of ERK itself[2]. SCH772984 has antitumor activity against BRAF or RAS mutations in cells that are resistant to native MAPK inhibition and those that are resistant to MAPK inhibition[3].
In vitro, 11 of 14 NRAS mutant melanoma cell lines treated with SCH772984 (0-10μM) for 72-120h were highly sensitive to SCH772984 with IC50<1μM[4]. SCH772984 (0-10μM) treated human non-small cell lung cancer cell line (NCI-H727 cells) for 6h and 24h downregulated the phosphorylation of ERK and other proteins in parental H727 cells and two MEK- and ERK-resistant sublines after 6h and 24h of treatment[5].
In vivo, SCH772984 (10mg/kg) treated with intraperitoneal injection in septic mice increased the survival rate of mice, reduced the plasma levels of Ccl2/Mcp1, inhibited molecular processes related to immune response and hemostasis in the kidney and liver, and activated the extracellular matrix (ECM) organization and retinoic acid (RA) signaling pathways in the lung and liver[6]. SCH772984 (0.1, 1.0, 10μg) was injected intrathecally to treat rats with tibial bone cancer pain model, producing analgesic effects in a dose-dependent manner and significantly reducing the expression of Fos protein in the dorsal horn of the spinal cord[7].
References:
[1] Morris E J, Jha S, Restaino C R, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors[J]. Cancer discovery, 2013, 3(7): 742-750.
[2] Li H, Wang C, Gong Z, et al. Transient Receptor Potential Ankyrin 1-dependent Activation of Extracellular Signal-regulated Kinase 2 in the Cerebral Cortices Contributes to Cortical Spreading Depolarization[J]. Neuroscience, 2024, 543: 90-100.
[3] Miao L, Tian H. Development of ERK1/2 inhibitors as a therapeutic strategy for tumour with MAPK upstream target mutations[J]. Journal of drug targeting, 2020, 28(2): 154-165.
[4] Wong D J L, Robert L, Atefi M S, et al. Antitumor activity of the ERK inhibitor SCH722984 against BRAF mutant, NRAS mutant and wild-type melanoma[J]. Molecular cancer, 2014, 13: 1-15.
[5] Moschos S J, Sullivan R J, Hwu W J, et al. Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors[J]. JCI insight, 2018, 3(4).
[6] Kopczynski M, Rumienczyk I, Kulecka M, et al. Selective extracellular signal-regulated kinase 1/2 (erk1/2) inhibition by the sch772984 compound attenuates in vitro and in vivo inflammatory responses and prolongs survival in murine sepsis models[J]. International Journal of Molecular Sciences, 2021, 22(19): 10204.
[7] Bian J, Zhu S, Ma W, et al. Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain[J]. Saudi Pharmaceutical Journal, 2016, 24(3): 354-362.
| Cell experiment [1]: | |
Cell lines | 14 NRAS mutant melanoma cells lines |
Preparation Method | All cell lines were treated in duplicates with 0-10μM of SCH772984, vemurafenib and trametinib alone or in combination and constant amount of DMSO for all the conditions. After incubation for 72-120h, the cell viability was determined. Each experiment was repeated independently at least 3 times. |
Reaction Conditions | 0-10μM; 72-120h |
Applications | All NRAS-mutant cell lines were resistant to vemurafenib, 11 of 14 were highly sensitive to SCH772984 (IC50<1μM). |
| Animal experiment [2]: | |
Animal models | C57BL/6W mice |
Preparation Method | C57BL/6W mice were induced with septic shock by lipopolysaccharide (LPS) (20mg/kg) or cecal ligation and puncture (CLP), respectively. In the LPS group, mice were injected intraperitoneally with 10mg/kg SCH772984 or formulation (3% DMSO+10% polyethylene glycol) 2h after administration, and then injected with SCH772984 every 6h. In the CLP experimental group, mice were injected intraperitoneally with 10mg/kg SCH772984 or formulation 2h after the CLP procedure. Mice received a single and double dose of SCH772984 at the 6-hour and 12-hour time points, respectively. Anesthesia was then induced with isoflurane and blood was collected by cardiac puncture. The chest cavity was opened, and the heart and lungs were quickly collected into cryovials and immediately snap-frozen in liquid nitrogen. The kidneys and liver were then immediately collected in the same manner. |
Dosage form | 10mg/kg, single and double dose at the 6-hour and 12-hour time points; i.p. |
Applications | SCH772984 treatment improved survival in the LPS-induced lethal endotoxemia and cecal ligation and puncture (CLP) mouse models of sepsis, and reduced plasma levels of Ccl2/Mcp1. |
References: [1]Wong D J L, Robert L, Atefi M S, et al. Antitumor activity of the ERK inhibitor SCH722984 against BRAF mutant, NRAS mutant and wild-type melanoma[J]. Molecular cancer, 2014, 13: 1-15. [2]Kopczynski M, Rumienczyk I, Kulecka M, et al. Selective extracellular signal-regulated kinase 1/2 (erk1/2) inhibition by the sch772984 compound attenuates in vitro and in vivo inflammatory responses and prolongs survival in murine sepsis models[J]. International Journal of Molecular Sciences, 2021, 22(19): 10204. | |
| Cas No. | 942183-80-4 | SDF | |
| Chemical Name | (3R)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide | ||
| Canonical 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 | ||
| Formula | C33H33N9O2 | M.Wt | 587.67 |
| Solubility | ≥ 14.7 mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7016 mL | 8.5082 mL | 17.0164 mL |
| 5 mM | 340.3 μL | 1.7016 mL | 3.4033 mL |
| 10 mM | 170.2 μL | 850.8 μL | 1.7016 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)