HBS-101 is a selectively, orally active, brain-penetrant, Midkine (MDK) inhibitor ( K D = 38.4 nM). HBS-101 significantly reduces cell viability, clonogenic survival, and invasiveness and increases apoptosis. HBS-101 involves suppression of the Akt/mTOR, STAT3, and NF-κB pathways. HBS-101 can be used for the study of Triple-negative breast cancer (TNBC) [1].
In Vivo, HBS-101 (1 mg/kg (i.v.), 10 mg/kg (p.o.) has rapid in vivo disposition kinetics and extremely high oral bioavailability in rats[1]. HBS-101 (10 mg/kg, i.p.) can be rapidly absorbed and effectively penetrates the blood-brain barrier in mice[1]. HBS-101 (2-10 mg/kg, p.o., 5 days) doses up to 10 mg/kg (oral) for 5 consecutive days are safe and do not produce observable organ toxicity in mice[1]. HBS-101 (2 mg/kg, 5 mg/kg, p.o., 5 days) effectively inhibits the growth of TNBC orthotopic tumors with oral administration, and 5 mg/kg is determined to be the minimum effective dose in mice[1]. HBS-101 (5 mg/kg, p.o., 5 days a week) reduces the proliferative activity of tumors in MDA-MB-231 cells xenograft mice[1]. HBS-101 (10 mg/kg, i.p., 5 days a week) exhibits potent anti-tumor activity in a brain metastasis model in mice[1].
In Vitro, HBS-101 (0.1-10 μM, 5 days) significantly reduces cell viability of TNBC cell lines[1]. HBS-101 (0-5 μM) reduces the colony-forming ability of TNBC cells in a dose-dependent manner[1]. HBS-101 (20 μM, 24 h) induces apoptosis in TNBC cells, but not in normal mammary epithelial cells[1]. HBS-101 (20 μM, 20 h) significantly reduces the expression of MDK receptors, specifically Notch2, in HCC-70 cells; inhibits downstream signaling pathways, including mTOR, STAT3, and NF-κB; and increases cleaved caspase-3 levels[1]. HBS-101 (20 μM, 24 h) downregulates MDK target genes and significantly reduces STAT3 and NF-κB reporter activity in TNBC cells that stably express these reporters[1].
References:
[1]. Mahajan M, et al. The Discovery and Characterization of HBS-101, a Novel Inhibitor of Midkine, as a Therapeutic Agent for the Treatment of Triple-Negative Breast Cancer. Mol Cancer Ther. 2025 Sep 2;24(9):1308-1319.
In Vivo, HBS-101 (1 mg/kg (i.v.), 10 mg/kg (p.o.) has rapid in vivo disposition kinetics and extremely high oral bioavailability in rats[1]. HBS-101 (10 mg/kg, i.p.) can be rapidly absorbed and effectively penetrates the blood-brain barrier in mice[1]. HBS-101 (2-10 mg/kg, p.o., 5 days) doses up to 10 mg/kg (oral) for 5 consecutive days are safe and do not produce observable organ toxicity in mice[1]. HBS-101 (2 mg/kg, 5 mg/kg, p.o., 5 days) effectively inhibits the growth of TNBC orthotopic tumors with oral administration, and 5 mg/kg is determined to be the minimum effective dose in mice[1]. HBS-101 (5 mg/kg, p.o., 5 days a week) reduces the proliferative activity of tumors in MDA-MB-231 cells xenograft mice[1]. HBS-101 (10 mg/kg, i.p., 5 days a week) exhibits potent anti-tumor activity in a brain metastasis model in mice[1].
In Vitro, HBS-101 (0.1-10 μM, 5 days) significantly reduces cell viability of TNBC cell lines[1]. HBS-101 (0-5 μM) reduces the colony-forming ability of TNBC cells in a dose-dependent manner[1]. HBS-101 (20 μM, 24 h) induces apoptosis in TNBC cells, but not in normal mammary epithelial cells[1]. HBS-101 (20 μM, 20 h) significantly reduces the expression of MDK receptors, specifically Notch2, in HCC-70 cells; inhibits downstream signaling pathways, including mTOR, STAT3, and NF-κB; and increases cleaved caspase-3 levels[1]. HBS-101 (20 μM, 24 h) downregulates MDK target genes and significantly reduces STAT3 and NF-κB reporter activity in TNBC cells that stably express these reporters[1].
References:
[1]. Mahajan M, et al. The Discovery and Characterization of HBS-101, a Novel Inhibitor of Midkine, as a Therapeutic Agent for the Treatment of Triple-Negative Breast Cancer. Mol Cancer Ther. 2025 Sep 2;24(9):1308-1319.