Related Experiment Video
Updated: May 23, 2025
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
UNC9426, a Potent and Orally Bioavailable TYRO3-Specific Inhibitor.
Deyu Kong1, Xiangbo Yang1, Samantha Judd2
1Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Researchers discovered a new drug, UNC9426, that inhibits TYRO3, a protein involved in platelet aggregation. This TYRO3 inhibitor shows potential for treating thrombosis without increasing bleeding risk.
Area of Science:
- Biochemistry
- Pharmacology
- Drug Discovery
Background:
- TYRO3 is a key protein that amplifies platelet aggregation.
- Selective TYRO3 inhibition offers a potential therapeutic strategy for thrombosis with reduced bleeding risk.
Purpose of the Study:
- To discover and characterize a novel, potent TYRO3 inhibitor.
- To evaluate the therapeutic potential of TYRO3 inhibition in preclinical models.
Main Methods:
- Employed a structure-based drug design approach.
- Discovered and characterized the TYRO3 inhibitor UNC9426.
- Assessed selectivity, pharmacokinetic properties, and in vivo efficacy in mouse models.
Main Results:
- Identified UNC9426 (12) as a potent TYRO3 inhibitor with excellent selectivity (S50 = 0.026).
- UNC9426 demonstrated favorable pharmacokinetic properties in mice.
- In vivo treatment with UNC9426 reduced platelet aggregation without increasing bleeding time.
Conclusions:
- UNC9426 is a promising TYRO3 inhibitor for treating thrombosis.
- TYRO3 inhibition also impacts tumor cells and macrophages, suggesting broader therapeutic applications.
- Selective TYRO3 inhibition presents a viable strategy for managing thrombosis and other diseases.
More Related Videos
10:49Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
09:15Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
Published on: October 20, 2022
