IC50: 27.8 nM (STAT3 luciferase activity)[1]
HP590 is an orally active, novel and potent STAT3 inhibitor (STAT3 luciferase activity: IC50=27.8 nM; ATP inhibition: IC50=24.7 nM). HP590 shows anti-proliferative activity to gastric cancer cells and induces apoptosis[1].
HP590 (0-40 μM; 72 h) shows anti-proliferative activities to MKN45, AGS, and MGC803 cells[1].
HP590 (0-40 nM; 0-24 h) inhibits STAT3 Tyr705 and Ser727 phosphorylation in GC cells, blocks the expression of STAT3 downstream genes (c-Myc and cyclin D1) in GC cells, reduces IL-6-mediated STAT3 nuclear translocation in MKN45 cells[1].
HP590 (5-20 nM; 48 h) induces gastric cancer cell apoptosis[1].
Cell Proliferation Assay[1]
| Cell Line: | MKN45, AGS, and MGC803 cells |
| Concentration: | 0-40 μM |
| Incubation Time: | 72 hours |
| Result: | Inhibited MKN45, AGS, and MGC803 cells with IC50s of 9.3, 13.5, and 8.7 nM, respectively. |
Apoptosis Analysis[1]
| Cell Line: | MKN45 and AGS cells |
| Concentration: | 5, 10, and 20 nM |
| Incubation Time: | 48 hours |
| Result: | Induced apoptosis in MKN45 and AGS cells in a dose-dependent manner. |
Western Blot Analysis[1]
| Cell Line: | Gastric Cancer Cells |
| Concentration: | 0-40 nM |
| Incubation Time: | 0-24 h |
| Result: | Inhibited STAT3 p-Tyr705 and p-Ser727 in GC cells completely at 40 nM. Blocked the expression of STAT3 downstream genes, including c-Myc and cyclin D1, in a concentration-dependent and time-dependent manner. Showed the STAT3 p-Tyr705 stimulated by IL-6 in GC cell lines, but entirely suppressed by HP590 at 40 nM. |
RT-PCR[1]
| Cell Line: | MKN45 and AGS cells |
| Concentration: | 10, 20, and 40 nM |
| Incubation Time: | 48 hours |
| Result: | Suppressed the expression of STAT3 downstream genes (c-Myc and cyclin D1) at the mRNA level. |
HP590 (oral administration; 25 and 50 mg/kg; once daily; 5 w) inhibits GC growth effectively by inhibiting the STAT3 activation and shows better tolerance in GC xenograft model[1].
| Animal Model: | BALB/c-nude mice injected with GC cells[1] |
| Dosage: | 25 and 50 mg/kg |
| Administration: | Oral administration; 25 and 50 mg/kg; once daily; 5 weeks |
| Result: | Inhibited MKN45 tumor growth in a concentration-dependent manner. Inhibited STAT3 phosphorylation at Tyr705 and Ser727 and reduced the expression of the downstream genes. Inhibited the expression of Ki67 (a proliferation marker). Showed no weight loss during HP590 treatment, and no apparent damage in the major organs of mice. |
[1]. He P, et al. Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr705/Ser727 Inhibitory Activity for Gastric Cancer Treatment. J Med Chem. 2022 Sep 14.