[CAS NO. 1782531-99-0] HLI373 dihydrochloride
PRODUCTS SPECIFICATIONS [1782531-99-0]
DESCRIPTION [1782531-99-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 414.33 |
| Molecular Formula | C18H25Cl2N5O2 |
| SMILES | O=C1N=C2N(C)C3=C(C=CC=C3)C(NCCCN(C)C)=C2C(N1C)=O.[H]Cl.[H]Cl |
Summary
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 IC
50
values (below 6 μM) against both chloroquine-sensitive
P. falciparum
D6 strain (
Pf
D6) and chloroquine-resistant
P. falciparum
W2 strain (
Pf
W2) 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]
.
MCE 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
References
- [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.