VX-11e
VX-11e is a potent and selective inhibitor of ERK [1].
ERK is extracellular signal-regulated kinases. The Ras/Raf/MEK/ERK signal transduction is an oncogenic pathway related to a variety of human cancers [1].
References:
[1]. Aronov, Alex M, Tang Q, et al. Martinez-Botella, Gabriel et al. Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control. Journal of Medicinal Chemistry, 2009, 52(20): 6362-6368.
- 1. Jinyang Cai, Sheeba Jacob, et al. "High-risk neuroblastoma with NF1 loss of function is targetable using SHP2 inhibition." Cell Rep. 2022 Jul 26;40(4):111095. PMID: 35905710
- 2. 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
- 3. Jingman Li, Yuchen Pan, et al. "Urokinase-type plasminogen activator receptor is required for impairing toll-like receptor 7 signaling on macrophage efferocytosis in lupus." Mol Immunol. 2020 Nov;127:38-45. PMID: 32911323
- 4. Zheng L, Guo Q, et al. "Transcriptional factor six2 promotes the competitive endogenous RNA network between CYP4Z1 and pseudogene CYP4Z2P responsible for maintaining the stemness of breast cancer cells." J Hematol Oncol. 2019 Mar 4;12(1):23. PMID: 30832689
- 5. Gao L, Guo Q, et al. "MiR-873/PD-L1 axis regulates the stemness of breast cancer cells." EBioMedicine. 2019 Feb 22. pii: S2352-3964(19)30112-4. PMID: 30803931
- 6. Kris Cameron Wood,Peter Saville Winter. "Compositions and Methods for Treating Cancer with JAK2 Activity." US Patent App. 15/027,216, 2016.
- 7. Zheng, Lufeng, et al. "The 3′ UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1." Breast cancer research and treatment (2015): 1-14. PMID: 25701119
- 8. Winter PS, et al. "RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis." Sci Signal. 2014 Dec 23. PMID: 25538080
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 500.35 |
| Cas No. | 896720-20-0 |
| Formula | C24H20Cl2FN5O2 |
| Synonyms | VX 11e, VX11e |
| Solubility | ≥25 mg/mL in DMSO; insoluble in H2O; ≥12.65 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[2-(2-chloro-4-fluoroanilino)-5-methylpyrimidin-4-yl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=CN=C(N=C1C2=CNC(=C2)C(=O)NC(CO)C3=CC(=CC=C3)Cl)NC4=C(C=C(C=C4)F)Cl |
| 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. |
| Kinase experiment [1]: | |
|
ERK inhibition assay |
Compounds were assayed for the inhibition of ERK2 by a spectophotometric coupled-enzyme assay. In this assay, a fixed concentration of activated ERK2 (10 nM) was incubated with various concentrations of the compounds in DMSO (2.5%) for 10 mins at 30 ℃ in 0.1 M HEPES buffer, pH = 7.5, containing 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 200 μM NADH, 150 μg/mL pyruvate kinase, 50 μg/mL lactate dehydrogenase and 200 μM erktide peptide. The reaction was initiated by the addition of 65 μM ATP. The rate of decrease of absorbance at 340 nM was monitored. The IC50 was evaluated from the data as a function of inhibitor concentration. |
| Cell experiment [1]: | |
|
Cell lines |
HT29 cells |
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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℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
≤ 10 μM; 48 hrs |
|
Applications |
In HT29 cells, VX-11e potently inhibited cell proliferation with an IC50 value of 48 nM. |
| Animal experiment [2]: | |
|
Animal models |
NSG mice bearing human melanoma RPDX tumors |
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Dosage form |
50 mg/kg; p.o.; b.i.d. |
|
Applications |
In NSG mice bearing human melanoma RPDX tumors, VX-11e (50 mg/kg, p.o.) potently inhibited pRSK and tumor growth. VX-11e, combined with BKM120, resulted in significantly improved tumor growth inhibition. |
|
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. |
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References: [1]. Aronov, Alex M, Tang Q, et al. Martinez-Botella, Gabriel et al. Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control. Journal of Medicinal Chemistry, 2009, 52(20): 6362-6368. [2]. Krepler C, Xiao M, Sproesser K, et al. Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies. Clin Cancer Res. 2016 Apr 1;22(7):1592-602. | |
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