EN4 is a covalent ligand designed to target cysteine 171 (C171) of MYC. It exhibits selectivity for c-MYC over N-MYC and L-MYC. Moreover, EN4 effectively inhibits MYC transcriptional activity.
体内研究
The administration of EN4 (50 mg/kg; intraperitoneal injection; daily; for 3 weeks) led to a significant reduction in tumor growth in 231MFP breast tumor xenograft mice[1].
体外研究
EN4 treatment at concentrations ranging from 1 to 50 μM for 72 hours markedly reduces proliferation of 231MFP breast cancer cells in a dose-dependent manner, achieving over 90% inhibition of proliferation at 50 μM[1].
EN4 treatment at a concentration of 50 μM for 60 hours significantly reduces the protein levels of representative MYC-regulated target genes, such as CDK2 and CDC25A. Additionally, EN4 treatment markedly decreases MYC levels[1].
EN4 demonstrates potent inhibition of both MYC/MAX binding to its DNA consensus sequence in vitro and MYC transcriptional activity in cells. It inhibits MYC/MAX binding to the E-box response element DNA consensus sequence in a dose-dependent manner, with an IC50 value of 6.7 μM. Additionally, EN4 inhibits MYC luciferase reporter activity in a dose-dependent manner, with an IC50 value of 2.8 μM[1].
EN4 treatment (50 μM; for 2 hours) resulted in a significant reduction in the thermal stability of MYC in 231MFP breast cancer cells[1].
EN4 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Trypanosoma brucei brucei (strain 427)
0.54 µM (IC50)
48 hours
Evaluate the growth inhibitory activity of the compound against T. b. brucei, with an EC50 of 0.54 μM.
Eur J Med Chem. 2024 Jan 5;263:115954.
Trypanosoma brucei gambiense (130R)
0.13 µM (IC50)
68 hours
Evaluate the growth inhibitory activity of the compound against T. b. gambiense, with an EC50 of 0.13 μM.
Eur J Med Chem. 2024 Jan 5;263:115954.
Trypanosoma brucei rhodesiense (STIB 900)
0.14 µM (IC50)
70 hours
Evaluate the growth inhibitory activity of the compound against T. b. rhodesiense, with an EC50 of 0.14 μM.
Eur J Med Chem. 2024 Jan 5;263:115954.
Human hepatocarcinoma cells (Hep G2, CRL-11997TM)
0.01–300 µM
72 hours
Evaluate the cytotoxicity of the compound against Hep G2 cells, with a CC50 >75 μM.
Eur J Med Chem. 2024 Jan 5;263:115954.
Mouse L929 fibroblasts
25, 50, 100 μg/mL
8 hours
To evaluate the cytotoxicity of EN4 on eukaryotic cells. EN4 exhibited time- and concentration-dependent cytotoxicity within the range of MBCs.
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