About

Xingui Liu joined the Department of Medicinal Chemistry at the College of Pharmacy, University of Florida, as an Assistant Professor in 2023. Her research focuses on proximity agents-based early drug discovery, including hit identification, lead optimization, and assay development. Prior to her current position, Dr. Liu was a Marie Skłodowska-Curie fellow in Prof. Alessio Ciulli’s lab at the Center for Targeted Protein Degradation (CeTPD), University of Dundee, where she developed PROTAC degraders of Leucine Rich Repeat Kinase 2 (LRRK2), a promising target for Parkinson’s disease. She also completed postdoctoral work at the University of Florida with Prof. Guangrong Zheng and Prof. Daohong Zhou, and earned her PhD at the University of Arkansas for Medical Sciences, where she designed, synthesized, and characterized delta-tocotrienol based radio-protectors. Her laboratory's research is at the interface of chemistry and biology, focusing on discovering and developing small molecules that target E3 ligases, promote protein-protein interactions, or induce protein degradation.

Research topics

• Chemistry
• Pharmacology
• Biochemistry
• Cancer research
• Biology
• Medicine
• Immunology
• Internal medicine
• Cell biology
• Computational biology
• Neuroscience
• Organic chemistry
• Psychology

Selected publications

• Enhancing semantic information of vector road networks using tile maps

  International Journal of Digital Earth · 2026-04-21

  articleOpen access

  Semantic information is a critical component of spatial data; however, it is often incomplete, limiting the usability of vector road networks. Tile maps are freely accessible, information-rich raster data containing complete road annotations. However, optical character recognition (OCR) applied to tile maps often produces fragmented text boxes and detects non-road text owing to resolution limitations and varying text orientations. To address these challenges, a method for enhancing the semantic information of vector road networks using tile maps is proposed in this study. The vector road network and tile maps are co-registered and segmented. An improved text extraction and merging strategy based on PaddleOCR is developed using geometric constraints to reconstruct fragmented road-name text. Furthermore, a geometry-constrained text classification model, termed the RoadSense Classifier, is introduced to filter non-road text and retain accurate road names. Matching the extracted road text to its corresponding road segments enriches the semantic information. Experiments using tile map data from the Third Ring Road area of Zhengzhou City and the main urban area of Xinxiang show that the proposed method achieves a precision of 98.86% and 97.64%, recall of 85.07% and 83.98%, and F1-score of 91.45% and 89.32%, respectively, improving vector road attribute completeness.

  PublisherDOI

• Discovery of Xz338, a Highly Potent Bcl-Xl Degrader

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Exploiting Avidity Effects for the Discovery of Low Affinity Protein-Binding Fragments

  Journal of Medicinal Chemistry · 2025-09-15 · 2 citations

  articleOpen access

  Fragment-based drug discovery (FBDD) is a powerful approach to the development of pharmaceuticals and probe molecules and there is broad interest in the development of new platforms for their discovery. Here, we introduce a workflow in which low molecular weight organic molecules displayed on the surface of TentaGel beads are exposed to a multimeric, fluorescently labeled target protein. Using tetrameric or dimeric protein targets, we show that beads that display even weak ligands (KDs in the high μM to low mM range) stably capture the protein due to avidity effects, thus allowing a simple “pull-down” protocol to be employed for fragment discovery. We also demonstrate that the platform is capable of supporting a “fragment growth” screen, which is a typical strategy to advance a fragment to a higher-affinity lead molecule. This platform is inexpensive and requires no specialized infrastructure.

  PublisherDOI

• Small-molecule degron mimetics for targeted protein degradation

  Essays in Biochemistry · 2025-10-22 · 1 citations

  articleOpen access1st authorCorresponding

  More than 80% of intracellular proteins are degraded by the ubiquitin-proteasome system. This system relies on a cascade of enzymes-E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin ligase)-to catalyze the polyubiquitination of target proteins, which are then recognized and degraded by the 26S proteasome. Among these enzymes, E3 ubiquitin ligases play a central role by specifically recognizing degron motifs on substrate proteins. The presence and accessibility of these degrons often dictate the half-life and stability of a given protein. Leveraging this mechanism, the artificial introduction of degrons or degron mimetics into otherwise stable proteins has emerged as a novel strategy in drug discovery for selectively degrading disease-causing proteins. In this short review, I will highlight small-molecule degron mimetics that have been developed for targeted protein degradation.

  PublisherOA PDFDOI

• Discovery of XZ338, a highly potent BCL-XL degrader

  European Journal of Medicinal Chemistry · 2025-04-15 · 5 citations

  articleOpen access

  specific inhibitor A-1331852, was generated. XZ338 is 70-fold more potent than ABT-263 against MOLT-4 T-ALL cells, with over 89-fold selectivity for MOLT-4 cells over human platelets.

  PublisherDOI

• Stereochemical inversion at a 1,4-cyclohexyl PROTAC linker fine-tunes conformation and binding affinity

  Bioorganic & Medicinal Chemistry Letters · 2024-06-26 · 8 citations

  articleOpen access

  Proteolysis targeting chimeras (PROTACs) are heterobifunctional small-molecule degraders made of a linker connecting a target-binding moiety to a ubiquitin E3 ligase-binding moiety. The linker unit is known to influence the physicochemical and pharmacokinetic properties of PROTACs, as well as the properties of ternary complexes, in turn impacting on their degradation activity in cells and in vivo. Our LRRK2 PROTAC XL01126, bearing a trans-cyclohexyl group in the linker, is a better and more cooperative degrader than its corresponding cis- analogue despite its much weaker binary binding affinities. Here, we investigate how this subtle stereocenter alteration in the linker affects the ligand binding affinity to the E3 ligase VHL. We designed a series of molecular matched pairs, truncating from the full PROTACs down to the VHL ligand, and find that across the series the trans-cyclohexyl compounds showed consistently weaker VHL-binding affinity compared to the cis- counterparts. High-resolution co-crystal structures revealed that the trans linker exhibits a rigid stick-out conformation, while the cis linker collapses into a folded-back conformation featuring a network of intramolecular contacts and long-range interactions with VHL. These observations are noteworthy as they reveal how a single stereochemical inversion within a PROTAC linker impacts conformational rigidity and binding mode, in turn fine-tuning differentiated propensity to binary and ternary complex formation, and ultimately cellular degradation activity.

  PublisherDOI

• Proximity-Based Modalities for Biology and Medicine

  ACS Central Science · 2023-07-14 · 176 citations

  reviewOpen access1st author

  Molecular proximity orchestrates biological function, and blocking existing proximities is an established therapeutic strategy. By contrast, strengthening or creating neoproximity with chemistry enables modulation of biological processes with high selectivity and has the potential to substantially expand the target space. A plethora of proximity-based modalities to target proteins via diverse approaches have recently emerged, opening opportunities for biopharmaceutical innovation. This Outlook outlines the diverse mechanisms and molecules based on induced proximity, including protein degraders, blockers, and stabilizers, inducers of protein post-translational modifications, and agents for cell therapy, and discusses opportunities and challenges that the field must address to mature and unlock translation in biology and medicine.

  PublisherOA PDFDOI

• Piperlongumine conjugates induce targeted protein degradation

  Cell chemical biology · 2023-02-01 · 70 citations

  articleOpen access
  PublisherOA PDFDOI

• Design and optimization of piperlongumine analogs as potent senolytics

  Bioorganic & Medicinal Chemistry Letters · 2023-12-15 · 4 citations

  article
  PublisherDOI

• Site-selection method of agricultural products logistics distribution centre based on blockchain

  International Journal of Information and Communication Technology · 2022-12-15 · 2 citations

  article1st authorCorresponding

  In order to overcome the problems of low on-time delivery rate and high distribution cost existing in the existing location methods of agricultural products logistics distribution centre, this paper proposes a new location method of agricultural products logistics distribution centre based on blockchain. Based on the analysis of the basic problems affecting the location of agricultural products logistics distribution centre, combined with the blockchain technology, the location model of agricultural products logistics distribution centre based on input-output ratio was constructed. Combining the idea of mountain climbing algorithm and particle swarm optimisation algorithm, the hybrid particle algorithm is used to solve the location model of agricultural products' logistics distribution centre, and the optimal location scheme is obtained. The experimental results show that the proposed method can effectively improve the on-time delivery rate, customer satisfaction, and reduce the logistics distribution costs. The maximum on-time delivery rate is 97.4%.

  PublisherDOI

Frequent coauthors

• Guangrong Zheng

  Yan'an Hospital Affiliated To Kunming Medical University

  38 shared

• Daohong Zhou

  The University of Texas Health Science Center at Houston

  35 shared

• Xuan Zhang

  30 shared

• Peiyi Zhang

  15 shared

• Dongwen Lv

  The University of Texas Health Science Center at San Antonio

  13 shared

• Yaxia Yuan

  The University of Texas Health Science Center at San Antonio

  13 shared

• Yonghan He

  Sichuan University

  12 shared

• Howard P. Hendrickson

  University of Arkansas for Medical Sciences

  11 shared

Labs

• Liu LaboratoryPI

Education

• Doctor of Philosophy

  University of Arkansas for Medical Sciences

  2018

• Master's Degree

  East China Normal University

  2014

• Bacherlor's degree

  China Pharmaceutical University

  2011