HS-173 inhibited the PI3K signaling pathway, and showed anti-proliferative effects on cancer cells. Also, HS-173 induced cell cycle arrest at the G(2)/M phase and apoptosis. In addition, HS-173 decreased the expression HIF-1α and VEGF which play an important role in angiogenesis. Furthermore, HS-173 diminished blood vessel formation in the Matrigel plug assay in mice. Combined treatment of Sorafenib and HS-173 synergistically inhibited the viability of Panc-1 cells (combination index<1). HS-173 demonstrated anti-proliferative effects in NSCLC cells and effectively inhibited the PI3K signaling pathway in a dose‑dependent manner.HS-173 reduced the expression of α-smooth muscle actin (α-SMA), vimentin, PAI-1, fibronectin, collagen type I, collagen IV and TGF-β-activated smad2/3 in PD-derived primary fibroblasts.
|Cell lines||T47D, SK-BR3, MCF7 cells|
|Preparation method||Using a MTT assay to performe cell viability . Briefly, plating T47D cells in 96-well plates for 24 h. Then,removing the medium and treating cells with either DMSO as a control or various concentrations of inhibitors. The final concentration of DMSO in the medium was ≤0.1% (v/v). After incubating the cells for 48 h, adding 20 μL MTT solution (5 mg/mL) to each well for another 4 h at 37 °C. The formazan crystals that formed are dissolved in DMSO (100 μL/well) by constant shaking for 5 min. Then read the plate on a microplate reader at 540 nm. Three replicate wells are used for each analysis. The median inhibitory concentration (IC50, defined as the drug concentration at which cell growth is inhibited by 50%) is assessed from the dose−response curves. To assess the effect of compounds on cell proliferation, culturing T47D cells with compound (0.1−100 μM) for 48 h before MTT analysis.|
|Incubation time||48 hours|
|Animal models||Male BALB/c mice with CCl4-induced liver fibrosis|
|Formulation||Dissolved in DMSO, and then mixture (DMSO:PEG400:D.W. = 1:5:4).|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Source||Oncotarget (2016). Figure 2. HS-173|
|Method||wound healing assay|
|Cell Lines||Miapaca-2 and Aspc-1 cells|
|Incubation Time||24 h|
|Results||In three pancreatic cancer cell lines, TGF-β treated group was healed over 90% of the wound area within 16 h, whereas cells in control group were slowly migrated. However, HS-173 successfully suppressed TGF-β induced cell migration dose-dependently in all pancreatic cancer cell lines|
HS-173, a Novel PI3K Inhibitor, Attenuates the Activation of Hepatic Stellate Cells in Liver Fibrosis.
Son MK, et al. Sci Rep. 2013 Dec 11;3:3470. PMID: 24326778.
A novel imidazopyridine PI3K inhibitor with anticancer activity in non-small cell lung cancer cells.
Lee H, et al. Oncol Rep. 2013 Aug;30(2):863-9. PMID: 23708425.
A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques.
Jung KH, et al. Int J Oncol. 2013 Jun;42(6):2001-8. PMID: 23588860.
Synergistic anticancer activity of HS-173, a novel PI3K inhibitor in combination with Sorafenib against pancreatic cancer cells.
Yun SM, et al. Cancer Lett. 2013 May 1;331(2):250-61. PMID: 23340175.
HS-173, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor, has anti-tumor activity through promoting apoptosis and inhibiting angiogenesis.
Lee H, et al. Cancer Lett. 2013 Jan 1;328(1):152-9. PMID: 22929971.
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