During the history of novel drug research and development, significant differences between mice, rats, dogs, monkeys and humans in drug absorption, distribution and excretion have resulted in massive losses and even total failures of drug application. Therefore, the availability of appropriate animals is critical for drug discovery.
In recent years, tree shrews (Tupaia belangeri chinensis) have attracted more and more attentions as a viable animal model in biomedical research due to its close affinity to primates, especially humans. As the first institute in China carries out researches and captive propagation of tree shrews, Kunming Institute of Zoology (KIZ), CAS has long being engaged in the studies of tree shrews. For example, in 2014, by cooperating with BGI, Shenzhen, KIZ has successfully analyzed the whole genome of Chinese tree shrews (Nature Communication 2013, 4, 1426).
Most recently, to systematically assess the characters and advantages of using tress shrews in pharmaceutical testing, based on the previous whole genomic data, Dr. ZHANG Yun and his research team developed a useful pipeline and stringent search strategy for large-scale genomic and transcriptomic screening of candidate proteins.
In this study, among the 3482 predicted drug targeting proteins, 446 and 1049 proteins were found with the highest rank and total scores, respectively, including homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Moreover, target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets.
This work not only provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research, but also demonstrates the feasibility of their newly developed strategy for large-scale drug target prediction and the evaluation of model-based target identification for drug testing.
The main findings have been published on PLoS One (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0104191)
(By Su-Qing Liu)