CAY10603

Cell lines

Pancreatic cancer cell lines, A549 and H460 cells, non-small cell lung cancer cells

Preparation method

The solubility of this compound in DMSO is >22.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.1 μM, 6 h

Applications

CAY10603 showed potent antiproliferative activity against pancreatic cancer cell lines with IC50 of <1 μM. CAY10603 was active against both the Mia Paca-2 and Panc04.03 cell lines at the 100 nM level and at the 200–300 nM level against HupT3. CAY10603 (0.1 μM, 6 h) blocked TNF-α-induced caspase-3 activation in endothelial cells. In HPAECs, pre-treated with CAY10603 (CAY, 0.1 μM) for 6 h inhibited TNF-α-induced endothelial permeability. CAY10603 (0.05 μM) significantly decreased the cell viability of NSCLC cells. In A549 and H460 cells, CAY10603 (0.01-0.16 μM) dose-dependently decreased total EGFR levels and the phosphorylation of EGFR, AKT, and ERK. In two human lung adeno-carcinoma cell lines: A549 and HCC827, CAY10603 treatment dose-dependently (0.02-0.32 μM) decreased cell proliferation. CAY10603 decreased clone numbers of the lung adenocarcinoma cell lines. CAY10603 clearly induced apoptosis in the lung adenocarcinoma cell line A549. Combination of CAY10603 (0.01 μM) and gefitinib (1 μM) for 48h remarkably inhibited the clono-genic survival of the A549 cells.

Animal models

C57BL/6 mouse model of endotoxemia

Dosage form

Intraperitoneal injection, 5 mg/kg, 2 h

Application

In a C57BL/6 mouse model of endotoxemia, pre-treatment with CAY10603 significantly inhibited endotoxin-induced caspase-3 activation and attenuated endotoxin-induced lung edema formation in the lung tissues.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Kozikowski, A. P., Tapadar, S., Luchini, D. N., Kim, K. H., & Billadeau, D. D. (2008). Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. Journal of medicinal chemistry, 51(15), 4370-4373.

[2]. Yu, J., Ma, M., Ma, Z., & Fu, J. (2016). HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions. Oncotarget, 7(34), 54714.

[3]. Wang, Z., Hu, P., Tang, F., & Xie, C. (2016). HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells. Medical Oncology, 33(5), 50.

[4]. Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., & Xie, C. (2016). HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma. Oncology reports, 36(1), 589-597.