| MPB3 | |
| Project ID |  MPB3 [Protein] |
| Project Theme | Structure and drug development of NPP family members involved in cancer and various diseases |
| Project Theme (short) | NPP family proteins |
| Principal Investigator | Junken Aoki |
| Affiliation | Graduate School of Pharmaceutical Sciences, Tohoku University |
| Backgrounds | - NPP enzyme family proteins are involved in extracellular metabolism - NPP proteins have been implicated in various diseases including cancers - Therefore, NPP family proteins are promising targets for therapeutic drug developments |
| Highlights | - We have succeeded in the structural analyses of NPP2 enzyme and its complexes with lysophosphatidic acids (LPAs) produced by NPP2 - We have identified compounds that inhibit the activity of NPP2 and NPP6 from eighty thousand compounds library screening - Our NPP2 inhibitors have exhibited striking therapeutic efficacy in lung and kidney fibrosis models |
| Outline | NPP (Ectonucleotide pyrophosphatase/phosphodiesterase) family proteins are involved in extracellular metabolism. Among 7 members of NPP family, we will target NPP1, NPP2 and NPP6 in this project. NPP1 regulates physiologic calcification. NPP2 (Autotaxin) generates the lipid signaling molecule lysophosphatidic acid (LPA). Because of its ability to stimulate cell proliferation, aberrant LPA-signaling has been linked to cancer. NPP6 produces choline that is an essential nutrient. Since choline and its metabolites are needed for such important physiological purposes as structural integrity and signaling roles for cell membranes and cholinergic neurotransmission, the choline deficiency play a role in liver disease, atherosclerosis and neurological disorders. Therefore, NPP family proteins are promising targets for therapeutic drug developments. We will tackle the difficult structure determination of NPPs which are the transmembrane proteins with long glycoprotein chains and try to find inhibitors for NPP1, NPP2 and NPP6. |
| Review | Curr. Med. Chem. |
| CSML File | MPB3.csml |