Integrate the Chinese Medicine Function and structure modification to develop new remedy for ulcerative colitis
Ulcerative Colitis (UC), which is one type of inflammatory bowel disease (IBD, another is Crohn’s Disease), is a chronic, progressive and disabling condition. There is no successful therapy that can treat UC so far. Remission maintenance, which is the key treat-to-target strategy’s endpoint of current practice. TNF-alpha inhibitors are currently recognised treat-to-target treatments for remission maintenance of UC. Unfortunately, more than 30% of patients do not respond to TNF-alpha inhibitor therapy, and 50% of responders can become tolerant to the drug and no longer respond to treatment within two years. There is an urgent need for developing new remedy for remission maintenance of UC.
Chinese herbal medicine has been used for UC in SCM clinics for long time, and helped many patients. Based on the clinical cases, and the literature reports, it is believed the effectiveness of herbal medicine should be thoroughly analyzed and find out the mechanism, further the results may help the drug discovery and drug development process.
In this proposed study, we will combine clinical data analysis, literature review, network pharmacological analysis, pharmacological analysis, and chemical structure modification study to find out the potential drug/compound pairs for UC treatment. The major components of the study involve the following aspects:
- Clinical data analysis: We have accumulated the sufficient data about UC treated with Chinese herbal medicine. Retrospectively, the clinical data could be analyzed and find out whether and how the herbs and fixed formulations are useful for the patients. Further, through network pharmacological study and pathway analysis, it is possible to find out the fixed herb pairs, compound pairs or combinations for UC treatment.
- Literature search: Based on our clinical data, the literature search will be conducted to find out whether and how the UC be treated with Chinese herbal medicine, at different stages.
- Pharmacological assessment: Based on the findings from the data analysis, the results will be validated in cell line, in vivo specific animal UC models to confirm the predictions through network pharmacological and clinical data analysis. These results will be helpful for the drug discovery and drug development.
- Structure Modification: Data from previous analysis could be the bases for the further structure modification, targeting on the hot drug targets in UC drug development, thus to enhance the drug safety and efficacy, supported by in vivo and in vitro data.
Through these steps, we wish to figure out the useful drug candidates for UC treatment.
Chinese medicine, Chemistry and new drug development.