Original story: UT Health San Antonio Newsroom
Discovery of chemical endocytosis could redefine precision medicine
Contact: Claire Kowalick, kowalick@uthscsa.edu
SAN ANTONIO (April 18, 2025) — A team of scientists, notably Zhengyu Wang, PhD, assistant professor in the department of pharmacology and the Barshop Institute, led by Hong-yu Li, PhD, professor of medicinal chemistry and chemical biology with the department of pharmacology and the Barshop Institute at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), together with two other teams led by Hui-kuan Lin, PhD, from Duke University (Duke) and Zhiqiang Qin, MD, PhD, from the University of Arkansas for Medical Sciences (UAMS), uncovered the mechanism of cellular uptake for large and polar drugs and devised a novel strategy to optimize the capacity of drug delivery into these cells.
Published online April 17, 2025, in Cell, the study creates a strategy called chemical endocytic medicinal chemistry that may revolutionize how endocytic drugs in the future are designed and developed. Other contributors to this publication include Bo-Syong Pan, PhD, Rajesh Manne, PhD, and Che-Chia Hsu, PhD, (Duke); Jungang Chen, PhD, Phuc Tran, PhD, Tsigereda Weldemichael, PhD, and Jingwei Shao, PhD, (UAMS); and Dongwen Lv, PhD, Minmin Wang, PhD, Wei Yan, PhD, assistant professor, Hongfei Zhou, PhD, Gloria M. Martinez, PhD, Robert Hromas, MD, FACP, dean of the Joe R. and Teresa Lozano Long School of Medicine and Daohong Zhou, MD, professor, associate director for drug development at the Mays Cancer Center and director of the Center for Innovative Drug Discovery (UT San Antonio).
“Chemical endocytic medicinal chemistry has the potential to impact every aspect of endocytic drugs from drug discovery and development to clinical practice,” said Li.
In this novel process, drug molecules are designed to better engage with CD36, a protein receptor found on the surface of many cells. By optimizing chemical interactions with CD36, the team was able to enhance the natural function of CD36, essentially escalating up the gateway for larger and polar drug compounds to enter the cell.
“This innovative chemical approach can potentially make any intravenous drug able to be taken orally. It can also promote any drug crossing the blood-brain barrier. This will remarkably broaden the number of agents we have to treat brain cancer or dementia,” said Robert A. Hromas, MD, FACP, dean of the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio.
Story continues:
UT Health San Antonio scientists pioneer drug-discovery breakthrough for large and polar drugs