Cell experiment:

The SW480 human colon adenocarcinoma and NIH3T3 mouse fibroblast cell lines are seeded in six-well plates at a density of 3×104 per well, grown for 36 to 48 hours, and then exposed to increasing concentrations of each compound (e.g., OSIP-486823; 1, 2 and 4 μM) for 48 hours. Cell numbers are determined using a Coulter counter and results are expressed as a percentage of the control culture. All assays are done in triplicate. Data are analyzed in Excel and the IC50s are determined graphically from cell survival curves[1].

OSIP-486823 is a novel microtubule-interfering agent with distinct biological effects on both protein kinase G (PKG) and microtubules.

OSIP486823 inhibits growth and induce apoptosis in SW480 human colon cancer cells, with IC50 of 0.1 μM. OSIP-486823 (OSIP486823) causes depolymerization of microtubules in interphase cells, inhibit spindle formation in mitotic cells, and induce multinucleated cells. Exisulind and the potent synthetic derivative OSIP-486823 are members of a new class of drugs known as selective apoptotic antineoplastic drugs that target cyclic guanosine 3′,5′-monophosphate phosphodiesterases (cGMP-PDE). OSIP-486823 also disrupts microtubule polymerization, perturbs mitotic spindle function, and arrests cells in mitosis in human glioma cells[1].

[1]. Xiao D, et al. The sulindac derivatives OSI-461, OSIP486823, and OSIP487703 arrest colon cancer cells in mitosis by causing microtubule depolymerization. Mol Cancer Ther. 2006 Jan;5(1):60-7.