Target Identification of a Novel Small Molecule Capable of Modifying Intervertebral Disc Degeneration
Grant Data
Project Title
Target Identification of a Novel Small Molecule Capable of Modifying Intervertebral Disc Degeneration
Principal Investigator
Dr Leung, Victor Yu Leong
(Principal Investigator (PI))
Co-Investigator(s)
Professor Chan Danny
(Co-Investigator)
Professor Cheung Kenneth Man Chee
(Co-Investigator)
Dr Sun Yi
(Co-Investigator)
Duration
13
Start Date
2021-03-01
Completion Date
2022-03-31
Amount
245700
Conference Title
Target Identification of a Novel Small Molecule Capable of Modifying Intervertebral Disc Degeneration
Keywords
A Novel Small Molecule, Capable Of Modifying, Intervertebral Disc Degeneration, Target Identification
Discipline
Others - Medicine, Dentistry and Health
HKU Project Code
InP/030/21
Grant Type
Research Talent Hub for ITF Projects (RTH-ITF)
Funding Year
2021
Status
Completed
Objectives
Despite the high prevalence of IDD in the elderly, there has been no therapeutics developed for alleviating IDD and that surgery, e.g. spinal fusion, is the only way to reduce the symptoms at the very late stage. Drug development is an important biotechnological component for treating IDD. We previously identified a novel compound termed TS17 that could suppress proteoglycan catabolism in IDD. Determination of its regulatory targets is indispensable for the clinical translation. By kinase profiling, we nailed three candidates of which activities were significantly inhibited. In this application, we hypothesize that specific kinase inhibition by TS17 is essential for modifying IDD. Objectives: 1) to characterize the biophysical interaction of TS17 with target kinases; 2) to validate the function of kinase inhibition in IDD. Methods: TS17-Kinases interaction will be elucidated by molecular docking and thermostability assay. TS17-mediated kinase inhibition will be profiled in cell culture and injury-induced mouse IDD. Furthermore, kinase inhibition by RNAi and IVD-specific knockout in a transgenic mouse will be established, and IDD attenuation will be evaluated. Significance: Identification and characterization of kinase inhibition as TS17 target will largely facilitate the downstream pharmaceutical translation, and ultimately reducing disability in the ageing population in Hong Kong and worldwide.