News Release

 Tokyo, Japan - March 18, 2003 - Yamanouchi Pharmaceutical Co., Ltd. (President: Toichi Takenaka) announced that it has discovered and identified three targets for drug screening in its cooperative research program with Metabolex, Inc. (President and Chief Executive Officer: Harold Van Wart, Ph.D.), CA, USA in the field of type 2 diabetes (insulin-resistant diabetes with impaired glucose tolerance) and obesity. These new targets were discovered in less than one year since the joint research program was started on a full scale.

The three targets discovered and identified include a membrane receptor, a functional protein, and a metabolic enzyme, and are all new target genes for drug discovery in the field of diabetes and obesity. Joint research results obtained to date have functionally verified that controlling these genes is useful for treating diabetes and obesity. It was discovered from Metabolex' proprietary human genome database containing DNA chip analysis data that the amount of the genes expressed for both the membrane receptor and the intrinsic ligand^*1 which binds to the receptor is significantly increased in patients with type 2 diabetes caused by the impairment of insulin function. Studies also showed that insulin resistance is improved as the amount of the gene's intrinsic ligand or the receptor is increased. These findings indicate that intracellular signals (information transmission) mediated by the gene's receptors enhance insulin's functions and that the expression of these genes increases in order to make up for decreases in insulin function due to decreases in the intrinsic ligand and/or receptors in type 2 diabetes patients. Therefore, a compound that binds with the receptors to make up for decreases in intrinsic ligand and inhibits the expression of increases genes as a result may become an effective drug for diabetes with a new mechanism of action. Function verification experiments showed that the two other genes are also promising as targets for the discovery of drugs for type 2 diabetes.

Yamanouchi plans to use these three genes as targets and start screening low-molecular-weight compounds that control their activity from its own library in order to accelerate the development of new drugs useful for diabetes and obesity. At present, new function verification experiments are underway in order to verify the usefulness of some more genes that may serve as targets for new drug development. In the joint research program with Metabolex, Yamanouchi intends to identify candidate compounds from at least 10 targets.

Yamanouchi gives a great strategic importance to genomic drug discovery and is promoting genomic drug discovery through 3 avenues (triangle approach): the gene-to-disease approach based on information on genes, the disease-to-gene approach based on information on diseases, and the compound-to-gene approach based on information on compounds. It is enthusiastically engaged in strategic alliances with research institutes and venture companies in Japan and abroad. As one of the strategic alliances, Yamanouchi signed a 3-year cooperative research agreement in March 2003 with Metabolex in the field of diabetes and obesity, which is one of the major fields for drug discovery research at Yamanouchi. Metabolex has spearhead technology in this field. Yamanouchi plans to use its Tsukuba Research Center as the hub in an effort to swiftly propel multifaceted drug discovery programs in order to win the ever-intensifying global genomics drug discovery race.