Catalog Number
ACM1276110065
Description
HS-173 is a potent PI3Kα inhibitor with potential anticancer activity. 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. This effect was confirmed by the suppression of tube formation and migration assay in vitro. Furthermore, HS-173 diminished blood vessel formation in the Matrigel plug assay in mice. Therefore, HS-173 is considered as a novel drug candidate to treat cancer patients.
Synonyms
HS173; HS 173; HS-173
IUPAC Name
ethyl 6-(5-(phenylsulfonamido)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxylate
Molecular Formula
C21H18N4O4S
Canonical SMILES
O=C(C1=CN=C2C=CC(C3=CC(NS(=O)(C4=CC=CC=C4)=O)=CN=C3)=CN21)OCC
InChI
InChI=1S/C21H18N4O4S/c1-2-29-21(26)19-13-23-20-9-8-15(14-25(19)20)16-10-17(12-22-11-16)24-30(27,28)18-6-4-3-5-7-18/h3-14,24H,2H2,1H3
InChI Key
SEKOTFCHZNXZMM-UHFFFAOYSA-N
Solubility
soluble in DMSO, not soluble in water
Appearance
White to off-white solid powder
Shelf Life
>2 years if stored properly
Storage
0-4 °C for short term (weeks to 1 month) or -20 °C for long terms (months to years).
Biological Target
HS-173 is a PI3Kα inhibitor with IC50 of 0.8 nM.
Drug Formulation
This drug may be formulated in DMSO
Elemental Analysis
C, 59.70; H, 4.29; N, 13.26; O, 15.15; S, 7.59
HS Tariff Code
2934.99.9001
In Vitro Activity
In order to evaluate the effect of HS-173 on the cell growth of pancreatic cancer, three cell lines (Panc-1, Miapaca-2 and Aspc-1) were used. When pancreatic cancer cells were treated with various concentrations (0.1-10 μM) of HS-173, it reduced the cell viability in a dose- and time-dependent manner (Figure 1A). In particular, 1 μM of HS-173 inhibited the cell growth by 40-50% in Miapaca-2 and Aspc-1 cells at 48 h. To further determine the sensitivity of HS-173, clonogenic assay was performed in Miapaca-2 cells for 14 days. In agreement with the MTT assay, HS-173 showed a significant drug response by the inhibition of colony formation in pancreatic cancer cells dose-dependently. Additionally, it was observed that colony formation by HS-173 was less than 50% in Miapaca-2 cells at dose of 1 μM (Figure 1B).
Reference: Oncotarget. 2016 Nov 22;7(47):78029-78047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363641/
In Vivo Activity
To determine whether HS-173 is involved in tumorigenesis in vivo, xenograft and orthotopic pancreatic tumor models were used in the Balb/c nude mice. HS-173 dramtically reduced tumor volume and weight, compared with the control group in two mouse models (Figure 6A and 6B). Also, HS-173 significantly increased expression of TUNEL, cleaved caspase-3 along with decreased expression of PCNA in tumor tissues (Figure 6C). To further confirm whether or not HS-173 inhibits tumor growth through the regulation of EMT, the expression levels of Ecadherin, Vimentin, ZEB1 along with p-AKT and p-Smad2 were identified. Ecadherin was increased, whereas Vimentin and ZEB1 were downregulated in the HS-173 treated group (Figure 6D and 6E). Furthermore, HS-173 treatment decreased p-AKT and p-Smad2 in tumor tissues. These results demonstrate that HS-173 has potent anti-tumor efficacy by inhibiting EMT via regulation of PI3K/AKT and TGF/Smads pathways.
Reference: Oncotarget. 2016 Nov 22;7(47):78029-78047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363641/
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Stock Solution Storage
0-4 °C for short term (days to weeks), or -20 °C for long term (months).
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