EN4 is a covalent ligand that targets cysteine 171 (C171) of MYC. EN4 is selective for c-MYC over N-MYC and L-MYC. EN4 inhibits MYC transcriptional activity, downregulates MYC targets, and impairs tumorigenesis.
体外研究
EN4 (1-50 μM; for 72 hours) treatment significantly impaires 231MFP breast cancer cell proliferation in a dosedependent manner, with >90% inhibition of proliferation at 50 μM.
EN4 (50 μM; for 60 hours) treatment significantly decreases the protein levels of representative MYC-regulated target genes, including CDK2 and CDC25A. EN4 treatment also substantially reduces MYC levels.
EN4 shows the strongest inhibition of both MYC/MAX binding to its DNA consensus sequence in vitro as well as MYC transcriptional activity in cells. EN4 inhibited MYC/MAX binding to the E-box response element DNA consensus sequence in a dose-responsive manner with an IC50 value of 6.7 μM. EN4 also inhibits MYC luciferase reporter activity in a dose-responsive manner with an IC50 value of 2.8 μM.
EN4 (50 μM; for 2 hours) treatment significantly reduced MYC thermal stability in 231MFP breast cancer cells.
Cell Proliferation Assay
Cell Line:
231MFP breast cancer cells
Concentration:
1 μM, 10 μM, 50 μM
Incubation Time:
72 hours
Result:
Significantly impaired 231MFP breast cancer cell proliferation in a dose-dependent manner.
Western Blot Analysis
Cell Line:
231MFP breast cancer cells
Concentration:
50 μM
Incubation Time:
60 hours
Result:
The protein levels of CDK2 and CDC25A were significantly lowered.
体内研究
EN4 (50 mg/kg; intraperitoneal injection; daily; for 3 weeks) treatment significantly attenuated tumor growth in 231MFP breast tumor xenograft mice.
Animal Model:
SCID mice injected with 231MFP breast cancer cells
Dosage:
50 mg/kg
Administration:
Intraperitoneal injection; daily; for 3 weeks
Result:
Significantly attenuated tumor growth in vivo.
分子式
C25H24N2O4
分子量
416.47
CAS号
1197824-15-9
运输条件
Room temperature in continental US; may vary elsewhere.