Research for Drug Discovery by THERAVALUES CORPORATION
THERAVALUES is currently conducting drug-discovery research in collaboration with universities and research institutions.
The research covers various subjects. Some typical topics are described below.
Pim-1&3 inhibitors
THERAVALUES has discovered compounds that simultaneously inhibit molecular target Pim-1 and Pim-3 kinases, and is investigating their anticancer activity. Pim-1&3 inhibitors are effective for various cancers, such as leukemia, liver cancer, and pancreatic cancer, and are expected to be next-generation anticancer drugs.
☆Pim kinases are phosphorylating enzymes (kinases) for intracellular proteins; three isoforms (Pim1, Pim2, and Pim3) are known.
Pim kinases control intracellular signaling of many physiologically active substances in order to regulate cell proliferation and survival.
Expression of Pim1 is especially high in malignant hematopoietic tumors. Pim3 is selectively activated in intractable pancreatic and liver cancers. Thus, Pim kinases are regarded as very attractive targets for the development of molecular target drugs for malignant tumors.
PPARγ agonist, aldose reductase inhibitor
THERAVALUES has discovered novel compounds that have two effects as therapeutic agents for type II diabetes, and is evaluating them in detail.
Two effects of the candidate compounds
Aldose reductase inhibitor
Aldose reductase 2 (which catalyzes sorbitol synthesis from glucose) is inhibited to suppress sorbitol accumulation.
→Diabetic complications are prevented and improved.
Representative drug: Epalrestat
PPARγ agonist
PPARγ enhances insulin sensitivity of tissues.
→Hyperglycemia is improved
Representative drug: Pioglitazone (Actos)
- Candidate antidiabetic drug effective for both diabetic hyperglycemia and its complications
- Side effects can be avoided because of its novel structure, which is unrelated to those of known drugs.
(Thiazolidine derivatives, which are conventional PPARγ agonists, pose a serious problem because they cause side effects such as obesity, edema, and cardiovascular toxicity.)
Curcumin analogs
THERAVALUES has synthesized many analogs of curcumin, from Curcuma long, and has studied their anti-inflammatory, anticancer, and antibacterial effects. Other potential candidates are under investigation.
Other research
THERAVALUES is planning to conduct research on anthelmintics that are effective against chloroquine-resistant malaria. THERAVALUES is also planning to evaluate the anti-influenza and anti-cytokine storm activity of thioredoxin.
Collaborators
Hokkaido University(Hokkaido), Tohoku University(Miyagi), Kyoto University(Kyoto), University of Toyama(Toyama), Akita University(Akita), Utsunomiya University(Tochigi), Kitasato University(Tokyo), Nagoya City University(Aichi), and others