ONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model.

Lysophosphatidic acid (LPA) is a bioactive lipid mediator that elicits a number of biological functions, including smooth muscle contraction, cell motility, proliferation, and morphological change. LPA is endogenously produced by autotaxin (ATX) from extracellular lysophosphatidylcholine (LPC) in plasma. Herein, we report our medicinal chemistry effort to identify a novel and highly potent ATX inhibitor, ONO-8430506 (), with good oral availability.

A novel highly potent autotaxin/ENPP2 inhibitor produces prolonged decreases in plasma lysophosphatidic acid formation in vivo and regulates urethral tension.

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), is a secreted enzyme that has lysophospholipase D activity, which converts lysophosphatidylcholine to bioactive lysophosphatidic acid. Lysophosphatidic acid activates at least six G-protein coupled recpetors, which promote cell proliferation, survival, migration and muscle contraction. These physiological effects become dysfunctional in the pathology of cancer, fibrosis, and pain.

Antimalarial activity of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic acid derivatives.

Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.

Detection of malaria parasites in mosquitoes from the malaria-endemic area of Chakaria, Bangladesh.

Malaria is one of the major public health problems of Bangladesh. We investigated the mosquito populations infected with malaria parasites in a malaria-endemic area Chakaria, Bangladesh, where Anopheles dirus and Anopheles minimus are the principal vectors. Anopheles mosquitoes were collected with a CDC miniature light trap from inside households in June 2007.

[A case report of infective endocarditis with acute pulmonary edema and renal dysfunction treated by emergent mitral valve replacement and postoperative extracorporeal ultrafiltration].

A 40-year-old woman with staphylococcus aureus endocarditis of the mitral valve associated with acute pulmonary edema and renal dysfunction is presented. The patient was admitted to Hiroshima University Hospital with infective endocarditis. On the 14th day after admission, she suffered from severe cardiac failure and oligouria, then she was transferred ICU.

Splenic vein thrombosis as a consequence of chronic pancreatitis: a study of three cases.

Splenic vein obstruction was found in three patients with chronic pancreatitis. All had suffered epigastric pain, but no specific findings which suggested obstruction of the splenic vein were evident on physical or laboratory examinations. Enlarged pancreatic contour with calculi and pseudocyst formation were observed by CAT scan in all three cases.