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SCH772984

Catalog No. T6066 CAS 942183-80-4

SCH 772984 is a potent inhibitor of ERK1/ERK2 (IC50: 4/1 nM) and has only weak inhibitory for other 300 tested kinases.

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SCH772984, CAS 942183-80-4

Pack Size	Availability	Price/USD
1 mg	In stock	$ 48.00
2 mg	In stock	$ 70.00
5 mg	In stock	$ 100.00
10 mg	In stock	$ 151.00
25 mg	In stock	$ 307.00
50 mg	In stock	$ 460.00
100 mg	In stock	$ 676.00
200 mg	In stock	$ 962.00
500 mg	In stock	$ 1,430.00
1 mL * 10 mM (in DMSO)	In stock	$ 133.00

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Purity: 98.75%

Purity: 98.45%

Purity: 98.01%

Purity: 98%

Purity: 97.65%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	SCH 772984 is a potent inhibitor of ERK1/ERK2 (IC50: 4/1 nM) and has only weak inhibitory for other 300 tested kinases.
Targets&IC50	ERK2:1 nM (cell free), ERK1:4 nM (cell free)
In vitro	SCH772984 potently inhibited ERK1 and ERK2 activity (IC50s: 4/1 nmol/L). SCH772984 is highly selective, with only seven kinases of 300 tested showing more than 50% inhibition at a concentration of 1 μmol/L. Treatment of the BRAFV600E-mutant human melanoma cell line LOXIMV1 (LOX) with SCH772984 resulted in a dose-dependent inhibition of phosphorylation of the ERK substrate p90 ribosomal S6 kinase. SCH772984 also inhibited phosphorylation of residues in the activation loop of ERK itself [1]. In a panel of 121 human tumor cell lines, SCH772984 showed EC50 values less than 500 nmol/L in approximately 88% and 49% of BRAF-mutant or RAS-mutant tumor lines, respectively [2].
In vivo	Treatment of BRAF-mutant LOX melanoma xenografts with SCH772984 (50 mg/kg twice daily) led to 98% tumor regression. Dose-dependent antitumor activity was also observed in the KRAS-mutant pancreatic MiaPaCa model, with 36% regression at 50 mg/kg twice daily [1].
Kinase Assay	SCH772984 was tested in 8-point dilution curves in duplicate against purified ERK1 or ERK2. The enzyme was added to the reaction plate and incubated with the compound before adding a solution of substrate peptide and ATP. Fourteen microliters of diluted enzyme (0.3 ng active ERK2 per reaction) was added to each well of a 384-well plate. The plates were gently shaken to mix the reagents and incubated for 45 minutes at room temperature. The reaction was stopped with 60 μL of IMAP Binding Solution (1:2,200 dilutions of IMAP beads in 1× binding buffer). The plates were incubated at room temperature for an additional 0.5 hours to allow complete binding of phosphopeptides to the IMAP beads. Plates were read on the LJL Analyst [1].
Cell Research	For resistant cell line creation, cells were grown in Dulbecco's modified Eagle medium with 10% heat-inactivated FBS media and increasing concentrations of inhibitor (PLX4032, 0.1–10 μmol/L; GSK1120212, 0.01–1 μmol/L) over approximately 4 to 8 months until resistant cells acquired growth properties similar to na?ve parental cells (at their top drug concentrations). For combination resistance, cells were incubated as above but with alternative dose escalation until a top concentration was acquired (PLX4032 10 μmol/L and GSK1120212 1 μmol/L). Stocks and dilutions of PLX4032, GSK1120212, and SCH772984 were made in DMSO solvent. Cell proliferation experiments were carried out in a 96-well format (six replicates), and cells were plated at a density of 4,000 cells per well. At 24 hours after cell seeding, cells were treated with DMSO or a 9-point IC50 dilution (0.001–10 μmol/L) at a final concentration of 1% DMSO for all concentrations. Viability was assayed 5 days after dosing using the ViaLight luminescence kit following the manufacturer's recommendations (n = 6, mean ± SE). For the cell line panel viability assay, cells were treated with SCH772984 for 4 days and assayed by the CellTiterGlo luminescent cell viability assay. For IncuCyte analysis, cells were plated as above in 96-well plates, and image-based cell confluence data were collected every 2 hours during live growth. For engineered resistant lines, cells were infected with lentivirus produced from lentiORF constructs expressing either RFP, KRASG13D, BRAFV600E, truncated BRAFV600E lacking exons 2–8 (Δ2-8), MEK1P124L, MEK1F129L, or constitutively active MEK1DD (S218D+S222D). Cells were selected in blasticidin (20 μg/mL) and used for ViaLight assays as described above [1].
Animal Research	Nude mice were injected subcutaneously with specific cell lines, grown to approximately 100 mm^3, randomized to treatment groups (10 mice/group), and treated intraperitoneally with either SCH772984 or vehicle according to the dosing schedule indicated in the figure legends. Tumor length (L), width (W), and height (H) were measured during and after the treatment periods by a caliper twice weekly on each mouse and then used to calculate tumor volume using the formula (L × W × H)/2. Animal body weights were measured on the same days twice weekly. Data were expressed as mean ± SEM. Upon completion of the experiment, vehicle- and SCH772984-treated tumor biopsies were processed for Western blot analysis [1].

Molecular Weight	587.67
Formula	C33H33N9O2
CAS No.	942183-80-4

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 51 mg/mL(86.8 mM)

References and Literature

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. 2. Chaikuad A, et al. A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics. Nat Chem Biol. 2014 Oct;10(10):853-60. 3. Jiang S, Wang Z, Zhu T, et al. The Downregulation of EIF3a Contributes to Vemurafenib Resistance in Melanoma By Activating ERK Via PPP2R1B[J]. 2021 4. Lang J Y, Wang X, Xie Q, et al. Targeting KRAS-mutant stomach/colorectal tumours by disrupting the ERK2-p53 complex[J]. bioRxiv. 2020 5. Chang G, Xiao W, Xu Z, et al. Pterostilbene Induces Cell Apoptosis and Cell Cycle Arrest in T-Cell Leukemia/Lymphoma by Suppressing the ERK1/2 Pathway[J]. BioMed Research International. 2017;2017:9872073 6. Zhang B, Zhao J, Wang Z, et al. DL0410 attenuates oxidative stress and neuroinflammation via BDNF/TrkB/ERK/CREB and Nrf2/HO-1 activation[J]. International Immunopharmacology. 2020, 86: 106729. 7. Bin Y F, Ma N, Lu Y X, et al. Erythromycin reverses cigarette smoke extract-induced corticosteroid insensitivity by inhibition of the JNK/c-Jun pathway[J]. Free Radical Biology and Medicine. 2020, 152: 494-503. 8. Xie D, Ge X, Ma Y, et al. Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway[J]. Journal of neuroinflammation. 2020, 17(1): 1-17. 9. Zhao Z, Xue F, Gu Y, et al. Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7, 8-dihydroxyflavone in female mice[J]. Molecular Metabolism. 2020: 101149. 10. Caiola E, Iezzi A, Tomanelli M, et al. LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitors.: ERK inhibitors in LKB1 mutated NSCLC[J]. Journal of Thoracic Oncology. 2019.

Citations

1. Wang X, Xie Q, Ji Y, et al.Targeting KRAS-mutant stomach/colorectal tumors by disrupting the ERK2-p53 complex.Cell Reports.2023, 42(1): 111972. 2. Lai J, Li Y, Ran M, et al.Xanthotoxin, a novel inducer of platelet formation, promotes thrombocytopoiesis via IL-1R1 and MEK/ERK signaling.Biomedicine & Pharmacotherapy.2023, 163: 114811. 3. Li M, Wang Z, Fu S, et al.Taurine reduction of injury from neutrophil infiltration ameliorates Streptococcus uberis-induced mastitis.International Immunopharmacology.2023, 124: 111028. 4. Jiang S, Wang Z, Zhu T, et al. The Downregulation of EIF3a Contributes to Vemurafenib Resistance in Melanoma By Activating ERK Via PPP2R1B. Frontiers in Pharmacology. 2021: 2242. 5. Zhang B, Zhao J, Wang Z, et al. DL0410 attenuates oxidative stress and neuroinflammation via BDNF/TrkB/ERK/CREB and Nrf2/HO-1 activation. International Immunopharmacology. 2020, 86: 106729. 6. Zhao Z, Xue F, Gu Y, et al. Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7, 8-dihydroxyflavone in female mice. Molecular Metabolism. 2020: 101149. 7. Caiola E, Iezzi A, Tomanelli M, et al. LKB1 Deficiency Renders NSCLC Cells Sensitive to ERK Inhibitors. Journal of Thoracic Oncology. 2020, 15(3): 360-370 8. Caiola E, Iezzi A, Tomanelli M, et al. LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitors.: ERK inhibitors in LKB1 mutated NSCLC. Journal of Thoracic Oncology. 2019 9. Chang Y W, Wang C C, Yin C F, et al. Quantitative phosphoproteomics reveals ectopic ATP synthase on mesenchymal stem cells to promote tumor progression via ERK/c-Fos pathway activation. Molecular & Cellular Proteomics. 2022, 21(6) 10. Yang J, Wang X, Fan Y, et al. Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression. Bioactive Materials. 2021

11. Zeng F, Li Y, Deng Z, et al. SARS‐CoV‐2 Spike Spurs Intestinal Inflammation via VEGF Production in Enterocytes. EMBO Molecular Medicine. 2022 May 9;14(5):e14844. doi: 10.15252/emmm.202114844. Epub 2022 Apr 19. 12. Xie D, Ge X, Ma Y, et al. Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway. Journal of neuroinflammation. 2020, 17(1): 1-17. 13. Bin Y F, Ma N, Lu Y X, et al. Erythromycin reverses cigarette smoke extract-induced corticosteroid insensitivity by inhibition of the JNK/c-Jun pathway. Free Radical Biology and Medicine. 2020, 152: 494-503 14. Chang G, Xiao W, Xu Z, et al. Pterostilbene Induces Cell Apoptosis and Cell Cycle Arrest in T-Cell Leukemia/Lymphoma by Suppressing the ERK1/2 Pathway. BioMed Research International. 2017;2017:9872073 15. Zhu F D, Wang B D, Qin D L, et al.Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease.CNS Neuroscience & Therapeutics.2023

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Related compound libraries

This product is contained In the following compound libraries：

Inhibitor Library Anti-Cancer Active Compound Library Highly Selective Inhibitor Library Osteogenesis Compound Library Anti-Aging Compound Library Oxidation-Reduction Compound Library HIF-1 Signaling Pathway Compound Library NO PAINS Compound Library Anti-Pancreatic Cancer Compound Library MAPK Inhibitor Library

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Keywords

SCH772984 942183-80-4 MAPK ERK MEK Extracellular signal regulated kinases Inhibitor inhibit SCH 772984 SCH-772984 inhibitor

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