Traf2- and Nck-interacting kinase (TNIK) is closely related to the cancer occurrence, development, and prognosis. TNIK plays an important role in regulating Wnt/β-catenin pathway, thus becoming a potential target for cancer treatment. Various small-molecule TNIK inhibitors with diverse structures and potent in vitro activities have been developed to treat tumors. However, no TNIK inhibitor has entered clinical phase mainly due to poor selectivity, toxicity, and unsatisfied in vivo anti-tumor efficiency. This review summarizes the research progress of small molecule inhibitors targeting TNIK, with the aim of giving some guidance for future research and development of small-molecule inhibitors.

OBJECTIVE: To explore effects of exercise on the expression of adiponectin mRNA and protein in visceral adipose tissue, plasma adiponectin concentration, and insulin resistance of aged obese rats. METHODS: Male SD rats age to 21 days old were fed with high-fat diet (fat percentage was 36.3% to 40.0%) for three stages of adolescence, maturity and old age to establish elderly obesity rats model. When the rats aged to 60 weeks old, natural growing elderly rats were randomly divided into control group (C) and aged exercise group (AE), =6; elderly obesity rats were randomly divided into obesity control group (OC) and obesity exercise group (OE), =6. The treadmill grade was 0°, the exercise speed and time were 15 m/min×15 min, 4 groups each time, between consecutive groups the rats had 5 minutes rest, the rats were exercised for 60 minutes every day, five days a week, continuous exercise for 8 weeks. Then, the expressions of adiponectin mRNA and protein in visceral adipose tissue were determined. The concentrations of blood glucose, plasma adiponectin and insulin were measured. Insulin resistance was calculated. RESULTS: Comparison with control group, the expressions of adiponectin mRNA and protein were obviously decreased, the concentration of blood glucose and insulin resistance were significantly increased in obesity control group, while the expressions of adiponectin mRNA and protein were obviously increased. Comparison with obesity control group, the expressions of adiponectin mRNA and protein, the concentration of plasma adiponectin were obviously increased, the concentration of blood glucose and insulin resistance were significantly decreased in obesity exercise group. CONCLUSIONS Adiponectin mRNA and protein expression in visceral adipose tissue is decreased and accompanied by high blood glucose and insulin resistance in elderly obesity rats. Exercise can increase the adiponectin mRNA and protein expression in visceral adipose tissue, elevate levels of plasma adiponectin, and decrease the level of blood glucose and insulin resistance in elderly obesity rats.
Adiponectin ; Adipose Tissue ; Animals ; Blood Glucose ; Insulin Resistance ; Male ; Obesity ; Rats ; Rats, Sprague-Dawley