Abstract 2593: A novel small molecule drug (LWKS) for pancreatic cancer therapy

Pancreatic ductal adenocarcinoma (PDAC) currently stands at approximately 29,000 new cases per year in North America and lack of effective therapies leads to an extremely poor prognosis. Since pancreatic cancers respond poorly to chemotherapy, more effective and less toxic treatment is a crucial need. We have employed a biological assay (MTS assay) to identify small molecular compounds that induce cytotoxicity specifically in pancreatic cancer cells and not in normal cells by screening large number of compounds from various combinatorial chemical library. Commercially available PDAC cells derived from various stages of pancreatic cancer were used for screening. For normal cells, immortalized epithelial cells isolated from pancreatic duct (h-tert HPNE) were used. One of the compounds, LWKS (MW: 547.94) kills pancreatic cancer cells and not the normal HPNE cells. LWKS kills pancreatic cancer cells isolated from all the four stages and the EC50 is in the range of 2 – 10 µM, whereas for normal cells is 70 µM. Maximum tolerated dose is 80 mg/kg of body weight. At 20 mg/Kg body weight, it showed significant tumor shrinkage in human PDAC xenografts mice model when compared to PBS controls. The tumor reduction was monitored by measuring the tumor volume for two times per week for 8 weeks. All the animal safety procedures were followed as described by AALAC. At this dosage level no toxicity was observed in the mice model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2593. doi:10.1158/1538-7445.AM2011-2593