HLI373 dihydrochloride is an efficacious Hdm2 inhibitor. HLI373 dihydrochloride inhibits the ubiquitin ligase activity of Hdm2. HLI373 dihydrochloride 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
414.33
Formula
C18H25Cl2N5O2
CAS 号
1782531-99-0
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.
