SCH772984
SCH772984, identified by an affinity-based mass spectroscopy high-throughput platform, is a novel, potent and ATP-competitive inhibition of ERK1 and ERK2 with 50% inhibition concentration IC50 values of 4 nmol/L and 1 nmol/L respectively. Although it displays behaviors of both type I and type II kinase inhibitors, SCH772984 is highly selective against only seven kinases, including CLK2, FLT4, GSG2, MAP4K4, MAPK1, MINK1, PRKD1 and TTK, out of a wide range of 300 tested with more than 50% inhibition at a concentration of 1 μmol/L. Study results have shown that SCH772984 potently inhibits tumor cells with mutations in BRAF, NRAS and KRAS at nanomolar concentrations.
Reference
Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A, Carr D, Deng Y, Jin W, Black S, Long B, Liu J, Dinunzio E, Windsor W, Zhang R, Zhao S, Angagaw MH, Pinheiro EM, Desai J, Xiao L, Shipps G, Hruza A, Wang J, Kelly J, Paliwal S, Gao X, Babu BS, Zhu L, Daublain P, Zhang L, Lutterbach BA, Pelletier MR, Philippar U, Siliphaivanh P, Witter D, Kirschmeier P, Bishop WR, Hicklin D, Gilliland DG, Jayaraman L, Zawel L, Fawell S, Samatar AA. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-750
- 1. Guoyue Lv, et al. "Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis." Nat Commun. 2024 Jan 27;15(1):807. PMID: 38280848
- 2. Jinchao Gao, Qingxiang Song, et al. "Intracerebral fate of organic and inorganic nanoparticles is dependent on microglial extracellular vesicle function." Nat Nanotechnol. 2024 Mar;19(3):376-386. PMID: 38158436
- 3. Shengliang Zhang, Lanlan Zhou, et al. "Small-molecule NSC59984 induces mutant p53 degradation through a ROS-ERK2-MDM2 axis in cancer cells." Mol Cancer Res. 2022 Jan 6. PMID: 34992144
- 4. Xin‐Li Liu, Wen‐Jing Liu, et al. "miR-506-loaded gelatin nanospheres target PENK and inactivate the ERK/Fos signaling pathway to suppress triple-negative breast cancer aggressiveness." Mol Carcinog. 2021 Aug;60(8):538-555. PMID: 34062009
- 5. Labuzan SA, Lynch SA, et al. "Inhibition of Protein Phosphatase Methylesterase 1 Dysregulates MAP Kinase Signaling and Attenuates Muscle Cell Differentiation." Gene. 2020;144515. PMID: 32112987
- 6. Liu B, Shen LJ, et al. "Automobile exhaust-derived PM(2.5) induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats." Ecotoxicol Environ Saf. 2020 Feb;189:110053. PMID: 31862514
- 7. Li J, Shi W, et al. "Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation." Nat Commun. 2019 Jul 29;10(1):3371. PMID: 31358760
- 8. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID: 31063758
- 9. Linnan Yang, Jing Sun, et al. "Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment." Advanced Science. 16 February 2019.
- 10. Wang Q, Zhi Y, et al. "Suppression of OSCC malignancy by oral glands derived-PIP identified by iTRAQ combined with 2D LC-MS/MS." J Cell Physiol. 2019 Jan 28. PMID: 30693510
- 11. Alhakeem SS, McKenna MK, et al. "Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity." J Immunol. 2018 Jun 15;200(12):4180-4189. PMID: 29712773
- 12. Li YY, Wu C, et al. "Degradation of AMPK-α1 sensitizes BRAF inhibitor-resistant melanoma cells to arginine deprivation." Mol Oncol. 2017 Dec;11(12):1806-1825. PMID: 29094484
- 13. Stark RJ, Koch SR, et al."Endothelial nitric oxide synthase modulates Toll-like receptor 4-mediated IL-6 production and permeability via nitric oxide-independent signaling." FASEB J. 2017 Oct 23. pii: fj.201700410R. PMID: 29061842
- 14. Ferraiuolo RM, Tubman J, et al. "The cyclin-like protein, SPY1, regulates the ERα and ERK1/2 pathways promoting tamoxifen resistance."Oncotarget. 2017 Apr 4;8(14):23337-23352. PMID: 28423577
- 15. Ying-Ying Li. "BRAF inhibitor (vemurafenib) resistance confers sensitivity to arginine deprivation in melanoma." University of Miami. May 2016.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 587.67 |
Cas No. | 942183-80-4 |
Formula | C33H33N9O2 |
Synonyms | SCH 772984; SCH-772984 |
Solubility | insoluble in EtOH; insoluble in H2O; ≥14.7 mg/mL in DMSO with gentle warming |
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 |
SDF | Download SDF |
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 |
Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
General tips | We do not recommend long-term storage for the solution, please use it up soon. |
Cell experiment [1]: | |
Cell lines |
melanoma cell lines (M408, M202, WM1366) |
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
Reaction Conditions |
24 h; 500 nM |
Applications |
Treatment with SCH772984 for the sensitive M408 resulted in decreased pRSK, disappearance of pERK1/2, and slight induction of pMEK, with no change in total RSK, MEK, ERK 1/2, or AKT. For the resistant M202, a modest induction of pMEK with some decrease in pERK and pRSK was observed at 24 hours. Treatment with SCH772984 resulted in upregulation of pAKT levels for M408 and WM1366. |
Animal experiment [2]: | |
Animal models |
Nude mice |
Dosage form |
25 mg/kg; b.i.d; intraperitoneal injection |
Applications |
The therapeutic effects of combining the CDK inhibitor Dinaciclib with inhibitors of ERK inhibitor SCH772984 were evaluated using two orthotopic patient-derived human pancreatic cancer xenograft models (Panc253 and Panc265). These models closely resemble the physiological and pathological conditions of pancreatic cancer in humans. A 2-3 mm3 tumor explant was implanted into the pancreas of nude mice and ultrasound imaging was used to measure the tumor size (3D) before randomization and treatment, which began when tumors grew to 50-100 mm3. The combination of Dinaciclib (20 mg/kg, i.p., t.i.w.) and SCH772984 (25 mg/kg, i.p., b.i.d.) dramatically inhibited the growth of primary orthotopic Panc265 (82.5%, p < 0.001) and Panc253 (95.7%, p |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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): 194. [2] Hu C, Dadon T, Chenna V, et al. Abstract B263: Combined inhibition of cyclin-dependent kinases (Dinaciclib) and AKT (MK-2206) or ERK (SCH772984) dramatically blocks pancreatic tumor growth and metastases in patient-derived orthotopic xenograft models[J]. Molecular Cancer Therapeutics, 2013, 12(11 Supplement): B263-B263. |
Description | SCH772984 is a novel, specific inhibitor of ERK1/2 with IC50 values of 4 nM and 1 nM, respectively. | |||||
Targets | ERK1 | ERK2 | ||||
IC50 | 4 nM | 1 nM |
Quality Control & MSDS
- View current batch: