HLI373 is an efficacious Hdm2 inhibitor. HLI373 inhibits the ubiquitin ligase activity of Hdm2. HLI373 is effective in inducing apoptosis of several tumor cells that are sensitive to DNA-damaging agents[1]. Antimalarial activity[2].
IC50 & Target
Hdm2[1]; Apoptosis[1]; Antimalarial[2]
体外研究 (In Vitro)
HLI373 (3-15 μM; 15 hours) selectively kills tumor cells harboring wild type p53[1]. HLI373 (10-50 μM) stabilizes cellular Hdm2 in a dose-dependent manner. HLI373 (3 μM) activates p53 transcription[1]. HLI373 selectively inhibits auto-ubiquitylation of Hdm2[1]. Co-transfection with plasmids encoding p53 and Hdm2 results in degradation of p53. Incubation with HLI373 (5-10 μM; 8 hours) blocks p53 degradation. HLI373 increases p53 and Hdm2 protein levels in cells[1]. HLI 373 also shows lower IC50 values (below 6 μM) against both chloroquine-sensitive P. falciparum D6 strain (PfD6) and chloroquine-resistant P. falciparum W2 strain (PfW2) and exhibits early growth inhibition[2]. HLI-373 is a MDM2 inhibitor interrupting its ubiquitin E3 ligase activity, could abolish the ubiquitylation of its substrate protein p53. HLI-373 targets the C-terminus functioning as an E3 ubiquitin ligase[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Wild type p53 mouse embryo fibroblasts (MEFs), and p53-deficient MEFs
Concentration:
3, 10, 15 μM
Incubation Time:
15 hours
Result:
Increased cell death in wild type p53 MEFs in a dose-dependent manner, p53-deficient MEFs were relatively resistant.
Western Blot Analysis[1]
Cell Line:
U2OS cells
Concentration:
5, 10 μM
Incubation Time:
8 hours
Result:
Blocked p53 degradation caused by co-transfection with plasmids encoding p53 and Hdm2.
分子量
341.41
Formula
C18H23N5O2
CAS 号
502137-98-6
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Jirouta Kitagaki, et al. Targeting Tumor Cells Expressing p53 With a Water-Soluble Inhibitor of Hdm2. Mol Cancer Ther. 2008 Aug;7(8):2445-54.
[2]. Jagrati Jain, et al. Inhibitors of Ubiquitin E3 Ligase as Potential New Antimalarial Drug Leads. BMC Pharmacol Toxicol. 2017 Jun 2;18(1):40.
[3]. Ying Chen, et al. MDM2 Promotes Epithelial-Mesenchymal Transition and Metastasis of Ovarian Cancer SKOV3 Cells. Br J Cancer. 2017 Oct 10;117(8):1192-1201.
