HJC0416 hydrochloride

HJC0416 hydrochloride is a potent and orally active STAT3 inhibitor with an enhanced anticancer profile than Stattic (HY-13818). HJC0416 hydrochloride is a promising anti-cancer agent for breast cancer study[1].

Signaling Pathways >> Stem Cell/Wnt >> STAT

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> STAT

STAT3

HJC0416 hydrochloride inhibits the proliferation of both ER-positive, and ER-negative (triple negative) breast cancer cells with IC50 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 IC50 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 (HY-13818) 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 (HY-13818). 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.

[1]. Haijun Chen, et al.Discovery of Potent Anticancer Agent HJC0416, an Orally Bioavailable Small Molecule Inhibitor of Signal Transducer and Activator of Transcription 3 (STAT3). Eur J Med Chem. 2014 Jul 23;82:195-203.