Skip to main content Skip to main menu
UF Health University of Florida
Department of Medicinal Chemistry College of Pharmacy
Research Overview

Liu Laboratory

Assistant Professor

Xingui Liu, Ph.D.

Research in the Liu lab focuses on discovering and characterization of small molecules that induce the degradation of disease-causing proteins.

UF College of Pharmacy in Gainesville
A graphic showing the sequence from PROTACs to target degradation.

Meet the Team

Xingui Liu

Department:

Medicinal Chemistry

Xingui Liu Ph.D.

Assistant Professor

Full Profile
Jason Jiang

Department:

Pharmaceutical Outcomes & Policy

Jason Jiang

Graduate Student

Full Profile
Eswarakumar Aratikatla

Department:

Medicinal Chemistry

Eswarakumar Aratikatla

Postdoctoral Associate

Full Profile

Former Members

Visiting Student

Jihyeon Yoon

Pharm.D. Student

Manh Nguyen

Visiting Scholar

Hirotake Furihata

Publications (updated Jan. 2025)

  1. (co-first author)  Kroupova, A., Rutter, Z., Hallatt, A. J., Ciulli, A.*, Stereochemical inversion at a 1, 4-cyclohexyl PROTAC linker fine-tunes conformation and binding affinity. Bioorg. Med. Chem Lett. 2024, 110, 129861.
  2. Zhang, X., He, Y., Liu, X., Zhang, X., Shi, P., Wang, Y., Zhou, D., Zheng, G.*, Design and Optimization of Piperlongumine Analogs as Potent Senolytics. Bioorg. Med. Chem Lett. 2024, 98, 129593.
  3. Liu, X., and Ciulli, A.*, Proximity-based modalities for biology and medicine. ACS Cent. Sci. 2023, 9, (7):1269–1284. invited outlook. DOI: 10.1021/acscentsci.3c00395. Listed as 1st Most Read Article in the journal (Aug 2023)
  4. Liu, X. (co-first author), Hu, W., Sohb, A., Yuan, Y., Zhou, S., Hua, N. Mackintosh, S.G., Zhang, X., Basso, K.B., Kamat, M., Yang, Q., Licht, J.D., Zheng, G.*, Zhou, D.*, Lv, D.* Piperlongumine conjugates induce targeted protein degradation. Cell Chem. Biol., 2023, 30(2):203-213.e17. DOI: org/10.1016/j.chembiol.2023.01.004. Piperlongumine was found to be able to engage with proteasome degradation machinery leading us to design Piperlongumine conjugates for targeted protein degradation.
  5. Liu, X., Kalogeropulou, A. F. (co-first author), Domingos, S., Makukhin, N., Nirujogi, R. S., Singh, F., Shpiro, N., Saalfrank, A., Sammler, E., Ganley, I. G., Moreira, R., Alessi, D. R.*, Ciulli., A.*, Discovery of XL01126: A Potent, Fast, Cooperative, Selective, Orally Bioavailable, and Blood–Brain Barrier Penetrant PROTAC Degrader of Leucine-Rich Repeat Kinase 2. J. Am. Chem. Soc, 2022, 144, 37, 16930–16952. DOI:10.1021/jacs.2c05499. Designed and characterized the first potent and selective LRRK2 PROTAC degrader with orally bioavailability and BBB permeability. Developed a new Nano-BRET assay for characterizing ternary binding affinity and ternary complex formation of PROTACs. Listed as the 3rd Most Read Article in the journal (1-month timeframe, Sept. 2022; Listed as one of the Most Read Articles in the journal within the 12-month timeframe (July 2023).
  6. Liu, X., Ciulli, A.*, DUB be good to me. Nat. Chem. Biol., 2022, 18 (4), 358-359. DOI: 10.1038/s41589-022-00978-9. Invited news & views
  7. Lv, D., Pal, P., Liu, X., Jia, Y., Thummuri, D., Zhang, P., Hu, W., Pei, J., Zhang, Q., Zhou, S., Khan, S., Zhang, X., Hua, N., Yang, Q., Arango, S., Zhang, W., Nayak, D., Olsen, S.K., Weintraub, S.T., Hromas, R., Konopleva, M., Yuan, Y., Zheng, G.*, Zhou, D.* Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity. Nat. Commun. 2021, 12 (1), 6896. DOI: 10.1038/s41467-021-27210-x
  8. Pal, P., Thummuri, D., Lv, D., Liu, X., Zhang, P., Hu, W., Poddar, S., Hua, N., Khan, S., Yuan, Y., Zhang, X., Zhou, D., Zheng, G.* Discovery of a novel BCL-XL PROTAC degrader with enhanced BCL-2 inhibition. J. Med. Chem, 2021. DOI: 10.1021/acs.jmedchem.1c00517 PROTACs co-targeting BCL-XL and BCL-2 were developed, with potential of targeting cancers driven by both BCL-XL and BCL-2.
  9. Zhang, P., Zhang, X., Liu, X., Khan, S., Zhou, D., Zheng, G.*, PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors. Explor. Target Antitumor Ther. 2020, 1:259-272. DOI: 10.37349/etat.2020.00017. Invited review.
  10. Liu, X.; Zhang, X., Lv, D.; Yuan, Y.; Zheng, G.; Zhou, D.*; Assays and Technologies for Developing Proteolysis Targeting Chimera. Future Med. Chem. 2020, 12(12), 1155-1179. DOI: 10.4155/fmc-2020-0073. Listed as one of the most-read articles on this journal.
  11. He, Y., Khan, S., Huo, Z., Lv, D., Zhang, X., Liu, X., Yuan, Y., Hromas, R., Xu, M., Zheng, G., Zhou, D.*; Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies. J. Hematol. Oncol. 2020 13 (1), 103. DOI: 10.1186/s13045-020-00924-z.
  12. Liu, X., Gao, Z., Fu, Q., Song, L., Hendrickson, H., Crooks, P., Zhang, P., Zhang, X., Zhou, D., Zheng, G.*, Deuteration of farnesyl terminal methyl groups of δ-tocotrienol and its effects on the metabolic stability and ability of inducing G-CSF production. Bioorg. Med. Chem. 2020, 28 (11), 11548. DOI: 10.1016/j.bmc.2020.115498. Deuteration was used as a medicinal chemistry strategy to improve the metabolic stability of δ-tocotrienol.
  13. He, Y.; Zhang, X.; Chang, J.; Kim, H-N.; Zhang, P.; Wang, Y.; Khan, S.; Liu, X.; Zhang, X.; Lv, D.; Li, W.; Thummuri, D.; Yuan, Y.; Elisseeff, J. H.; Campisi, J.; Almeida, M.; Zheng, G.*; Zhou, D.* Using proteolysis targeting chimera technology to overcome ABT263 on-target platelet toxicity and improve its senolytic activity. Nat. Commun. 2020, 11 (1), 1996. DOI: 10.1038/s41467-020-15838-0.
  14. Zhang, X.; Thummuri, D.; Liu, X.; Khan, S.; He, Y.; Zhang, P.; Hu, W.; Yuan, Y.; Zhou, D.; Zheng, G.* Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity. Eur. J. Med. Chem. 2020, 192, 112186. DOI: 10.1016/j.ejmech.2020.112186.
  15. Liu, X.; Poddar, S.; Song, L.; Hendrickson, H.; Zhang, X., Yuan, Y.; Zhou, D.; Zheng, G.* Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluoro-Substituted δ-Tocotrienol Derivative. ChemMedChem 2020, 15 (6), 506-516. DOI: 10.1002/cmdc.201900676. An example shows that fluorine substitutions failed to improve the metabolic stability of a compound.
  16. Zhang, X.; Liu, X.; Zhou, D.; Zheng, G.* Targeting anti-apoptotic BCL-2 family proteins for cancer treatment. Future Med. Chem. 2020, 12(7), 563-565.  DOI: 10.4155/fmc-2020-0004. Invited review.
  17. Khan, S.; Zhang, X.; Lv, D.; Zhang, Q.; He, Y.; Zhang, P.; Liu, X.; Thummuri, D.; Yuan, Y.; Wiegand, J.;  Pei, J.; Zhang, W.; Sharma, A.; McCurdy, C.R.; Kuruvilla, V.M.;  Baran, N.; Ferrando, A.A.; Kim, Y.;  Rogojina, A.; Houghton, P.J.; Huang, G.; Hromas, R.; Konopleva, M.; Zheng, G.*, Zhou, D.*, A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat. Med. 2019, 25 (12), 1938-1947. DOI: 10.1038/s41591-019-0668-z. The BCL-XL PROTAC developed in this paper overcame the platelet toxicity associated with BCL-XL inhibition and is currently in phase 1 clinical trial (NCT04886622).
  18. Zhang, X.; Thummuri, D.; He, Y.; Liu X.; Zhang, P.; Zhou, D.; Zheng G.* Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL. Chem. Commun. 2019, 55 (98), 14765-14768. DOI: 10.1039/c9cc07217a.
  19. Zhang, X.; Zhang, S.; Liu, X.; Wang, Y.; Chang, J.; Zhang, X.; Mackintosh, SG.; Tackett, AJ.; He, Y.; Lv, D.; Laberge, RM.; Campisi, J.; Wang, J.; Zheng, G.*; Zhou, D.* Oxidation resistance 1 is a novel senolytic target. Aging cell 2018, 17 (4), e12780. DOI: 10.1111/acel.12780. The target identification for the senolytic agent we discovered.
  20. Liu, X.; Wang, Y.; Zhang, X.; Gao, Z; Zhang, S., Shi, P., Zhang, X., Song, L.; Hendrickson, H.; Zhou, D., Zheng, G.*, Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation. Bioorg. Med. Chem. 2018, 26 (14), 3925-3938. DOI: 10.1016/j.bmc.2018.06.013. Structural activity relationship study of piperlongumine analogues led to the discovery of a senolytic agent with improved potency.
  21. Che, R.; Liu, X. (Co-first author); Lu, W.* Synthesis of 1,3,4,6-Tetra-O-Acetyl-l-Gulose. Chin. J. Chem. 2017, 35 (2), 237–241. DOI: 10.1002/cjoc.201600658.
  22. Liu, X.; Gujarathi, S.; Zhang, X.; Shao, L.; Boerma, M.; Compadre, C. M.; Crooks, P. A.; Hauer-Jensen, M.; Zhou, D.; Zheng, G.* Synthesis of (2R,8′S,3′E)-δ-Tocodienol, a Tocoflexol Family Member Designed to Have a Superior Pharmacokinetic Profile Compared to δ-Tocotrienol. Tetrahedron 2016, 72 (27), 4001–4006. DOI: 10.1016/j.tet.2016.05.028. The semi-synthesis of δ-Tocodienol using multiple C-C coupling techniques.
  23. Wang, Y.; Chang, J.; Liu, X.; Zhang, X.; Zhang, S.; Zhang, X.; Zhou, D.*; Zheng, G.* Discovery of Piperlongumine as a Potential Novel Lead for the Development of Senolytic Agents. Aging (Albany NY) 2016, 8 (11), 2915–2926. DOI: 10.18632/aging.101100. The discovery of the second senolytic agent, piperlongumine, and the mechanism study.
  24. Gujarathi, S.; Liu, X.; Song, L.; Hendrickson, H.; Zheng, G.* A Mild and Efficient AgSbF6-Catalyzed Synthesis of Fully Substituted Pyrroles through a Sequential Propargylation/Amination/Cycloisomerization Reaction. Tetrahedron 2014, 70 (34), 5267–5273. DOI: 10.1016/j.tet.2014.05.073.