HS-173

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.

Product information

CAS Number: 1276110-06-5

Molecular Weight: 422.46

Formula: C21H18N4O4S

Synonym:

HS173

HS 173

HS-173

Chemical Name: ethyl 6-(5-(phenylsulfonamido)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxylate

Smiles: CCOC(=O)C1=CN=C2C=CC(=CN21)C1=CN=CC(=C1)NS(=O)(=O)C1C=CC=CC=1

InChiKey: SEKOTFCHZNXZMM-UHFFFAOYSA-N

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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

HS-173 (0.1-10 μM) reduces the cell viability in a dose- and time-dependent manner. HS-173 shows a significant drug response by the inhibition of colony formation in pancreatic cancer cells dose-dependently. HS-173 inhibits TGF-β-induced cell migration and invasion in pancreatic cancer cells. HS-173 suppresses TGF-β-induced epithelial mesenchymal transition (EMT). HS-173 treatment reduces cell viability in two hepatic stellate cell lines in a dose and time dependent manner. HS-173 induces cell cycle arrest in the G2/M phase. HS-173 treatment increases the expression of cleaved caspase-3 and decreased that of Bcl-2 in the HSC-T6 cells. HS-173 inhibits the expression of profibrotic mediators and ECM degradation modulators in HSCs[2]. The combination of Sorafenib and HS-173 synergistically inhibits cell proliferation in pancreatic cancer cell lines. The combination of Sorafenib and HS-173 inhibits key enzymes in both RAF/MAPK and PI3K/AKT signaling pathways.

In Vivo:

HS-173 (10 mg/kg, i.p.) significantly increases expression of TUNEL, cleaves caspase-3 along with decreased expression of PCNA in tumor tissues. HS-173 treatment decreases p-AKT and p-Smad2 in tumor tissues. HS-173 (10 and 30 mg/kg) significantly decreases the metastatic burdens on the lung and liver. HS-173 (10 and 20 mg/kg) inhibits ECM accumulation and PI3K/Akt signaling in mice with CCl4-induced liver fibrosis animal model. HS-173 clearly suppresses the expression of p-Akt and p-P70S6K along with decreasing expression of collagen I and vimentin in the mice with CCl4-induced liver fibrosis.

References:

1. Lee H, Kim SJ, Jung KH, Son MK, Yan HH, Hong S, Hong SS. A novel imidazopyridine PI3K inhibitor with anticancer activity in non-small cell lung cancer cells. Oncol Rep. 2013 Aug;30(2):863-9. doi: 10.3892/or.2013.2499. Epub 2013 May 27. PubMed PMID: 23708425.
2. Jung KH, Ryu YL, Lee HS, Lee H, Son MK, Yan HH, Hong SW, Ryu JK, Hong S, Suh JK, Hong SS. A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques. Int J Oncol. 2013 Jun;42(6):2001-8. doi: 10.3892/ijo.2013.1905. Epub 2013 Apr 16. PubMed PMID: 23588860.

Products are for research use only. Not for human use.