502137-98-6
502137-98-6 結(jié)構(gòu)式
基本信息
Pyrimido[4,5-b]quinoline-2,4(3H,10H)-dione, 5-[[3-(dimethylamino)propyl]amino]-3,10-dimethyl-
5-[[3-Dimethylamino)propyl]amino]-3,10-dimethylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dionedihydrochloride
常見(jiàn)問(wèn)題列表
Hdm2; Apoptosis; Antimalarial
HLI373 (3-15 μM; 15 hours) selectively kills tumor cells harboring wild type p53.
HLI373 (10-50 μM) stabilizes cellular Hdm2 in a dose-dependent manner.
HLI373 (3 μM) activates p53 transcription.
HLI373 selectively inhibits auto-ubiquitylation of Hdm2.
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.
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.
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.
Cell Viability Assay
| 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
| 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. |