ZSTK3744

ZSTK3744 is an aryl hydrocarbon receptor ( AhR ) agonist. ZSTK3744 directly binds to AhR, upregulates the expression of AhR target genes including CYP1A1, CYP1B1 and TIPARP, and mediates cell growth inhibitory activity in triple-negative breast cancer cells. ZSTK3744 induces apoptosis in triple-negative breast cancer cells. ZSTK3744 exhibits anti-tumor activity and can be used in the research of chemoresistant triple-negative breast cancer ^[1].

In Vivo, ZSTK3744 (2.5-10 mg/kg; i.v.; on days 0, 7, and 14) exerts significant, dose-dependent tumor growth inhibition effects in a Doxorubicin -resistant triple-negative breast cancer (TNBC) mouse xenograft model^[1]. ZSTK3744 (1-5 mg/kg; i.v.; on days 0, 4, and 8) inhibits tumor growth in parental triple-negative breast cancer (TNBC) mouse xenograft models^[1].

In Vitro, ZSTK3744 (0.1-1000 nM; 72 h) (compound 12) potently inhibits the growth of MDA-MB-468 triple-negative breast cancer (TNBC) cells, with an IC₅₀ of 0.87 nM^[1]. ZSTK3744 (0.1-1000 nM; 72 h) potently inhibits the growth of Doxorubicin -resistant MDA-MB-468/AR triple-negative breast cancer (TNBC) cells, with an IC₅₀ of 0.92 nM^[1]. ZSTK3744 (0.1-1000 nM; 72 h) inhibits the growth of Paclitaxel -resistant MDA-MB-468/PR triple-negative breast cancer (TNBC) cells with an IC₅₀ of 23.54 nM^[1]. ZSTK3744 (1-24 h) upregulates the mRNA expression of CYP1A1 and TIPARP in MDA-MB-468 triple-negative breast cancer (TNBC) cells in a time-dependent manner, with significant induction observable as early as 1 hour after treatment^[1]. ZSTK3744 (24 h) induces apoptosis in MDA-MB-468 TNBC cells, and its cell growth inhibitory activity is mediated at least partially via the caspase-dependent apoptotic pathway^[1]. ZSTK3744 (0.1-1000 nM; 72 h) potently inhibits the growth of MDA-MB-453 triple-negative breast cancer (TNBC) cells, with an IC₅₀ of 1.14 nM^[1]. ZSTK3744 (0.1-1000 nM; 72 h) potently inhibits the growth of DU4475 triple-negative breast cancer (TNBC) cells, with an IC₅₀ of less than 0.50 nM^[1]. ZSTK3744 (0.1-1000 nM; 72 h) exerts no significant inhibitory effect on the growth of Hs578T TNBC cells, with an IC₅₀ >500 nM^[1].

References:
[1]. Ohashi T, et al. ZSTK3744, a Novel Aryl Hydrocarbon Receptor Agonist, Exhibits Efficacy against Chemotherapy-Resistant Triple-Negative Breast Cancer. Cancer Res Commun. 2026;6(2):421-436.