HJC0416 hydrochloride, a potent, orally active inhibitor of STAT3, exhibits a superior anticancer profile compared to Stattic. It stands out as a promising agent for breast cancer research.

HJC0416 hydrochloride inhibits the proliferation of both ER-positive, and ER-negative (triple negative) breast cancer cells with IC 50 values of 1.76 μM and 1.97 μM, respectively. However, it displays a marked antiproliferative effect against pancreatic cancer cell line AsPC1 and Panc-1 with IC 50 values of 40 nM and 1.88 μM, respectively[1].HJC0416 hydrochloride (1-10 μM; 48 hours) inhibits cell growth and induced apoptosis accompanying cellular morphological changes in MDA-MB-231 breast cancer cells[1].HJC0416 hydrochloride (5 μM; 24 hours) decreases the STAT3 promoter activity by approximately 51%, while stattic only decreases the STAT3 promoter activity by 39% in MDA-MB-231 cells after transient transfecting with pSTAT3-Luc vector[1].HJC0416 hydrochloride (1-10 μM; 12 hours) has a comparable potency in downregulating STAT3 protein production and phosphorylation at Tyr-705 site when compares with Stattic. Additionally, it also induces cleaved caspase-3 and downregulated cyclin D1 levels in MDA-MB-231 cells[1]. Cell Cycle Analysis[1]Cell Line: MDA-MB-231 breast cancer cells Concentration: 1-10 μM Incubation Time: 48 hours Result: Induced cell apoptosis in cancer cells. Apoptosis Analysis[1]Cell Line: MDA-MB-231 breast cancer cells Concentration: 1 μM; 5 μM; 10 μM Incubation Time: 12 hours Result: Decreased p-STAT3 phosphorylation expression and cyclin D1 level.

HJC0416 hydrochloride (intraperitoneal injection; 10 mg/kg; 7 days) shows a 67% decrease of tumor volume as compared to the control mice. Similarly, HJC0416 hydrochloride (oral administration; 100 mg/kg; 14 days) also significantly reduces tumor volume at a dose of 100 mg/kg by 46%. The i.p. route appeared to have a better reduction of tumor volume. It is also noteworthy that HJC0416 does not show significant signs of toxicity at a dose of 100 mg/kg[1]. Animal Model: Mice with MDA-MB-231 cells[1]Dosage: 10 mg/kg (i.p.); 100 mg/kg (oral) Administration: Intraperitoneal injection, 7 days; oral administration, 14 days Result: Exhibited antitumor effects in the MDA-MB-231 triple-negative breast cancer murine xenograft model.