Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: oxadiazolyl ketones.

Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure-activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described.

Design and synthesis of oxime ethers of alpha-acyl-beta-phenylpropanoic acids as PPAR dual agonists.

Oxime ethers of alpha-acyl-beta-phenylpropanoic acids were prepared to apply as PPARalpha and gamma dual agonists. Among them, compound 11l proved to exhibit potent in vitro activities with EC(50) of 19 and 13nM in PPARalpha and gamma, respectively. It showed better glucose lowering effects than rosiglitazone 1 and ameliorated the lipid profile like plasma triglyceride in db/db mice model.

Upregulation of FLIP(S) by Akt, a possible inhibition mechanism of TRAIL-induced apoptosis in human gastric cancers.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in some, but not all cancer cells. To assess the regulation of TRAIL-resistance in the human gastric cancer cells, we examined TRAIL sensitivity, TRAIL receptor expression, and intracellular signaling events induced by TRAIL. All the gastric cancer cell lines tested were susceptible to TRAIL to some extent, except for SNU-216 cell line, which was completely resistant.

Manganese superoxide dismutase expression correlates with chemosensitivity in human gastric cancer cell lines.

Purpose: The purpose is to investigate the potential correlation between antioxidant enzyme (AOE) levels and resistance to anticancer drugs in human gastric carcinoma cell lines.

Experimental Design: Protein contents of AOEs such as manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase, catalase, glutathione S-transferase-pi, p-glycoprotein, and multidrug resistance-associated protein were observed by Western blot analysis, and MnSOD activity was measured in six Korean gastric cancer cell lines. The direct correlation between AOEs and the chemosensitivity to doxorubicin (DOX), mitomycin C, 5-fluorouracil, and vinblastine was analyzed by cytotoxicity test.

Manganese superoxide dismutase expression correlates with a poor prognosis in gastric cancer.

Objective: The biologic significance of superoxide dismutase (SOD) in transformed gastric carcinoma cells is unclear. The aim of this study was to examine the role of SOD as a prognostic indicator of gastric carcinomas and its association with other clinicopathological factors.

Methods: Expression of MnSOD and Cu/ZnSOD was evaluated immunohistochemically in gastric carcinomas and adenomas using tissue-array methods.