Research Lab

Chemical Biology

Chemical inducers of proximity (e.g. molecular glues and bifunctional molecules) are powerful chemical biology tools for the precise and temporal control of various cellular processes. We create these molecules for investigating the posttranslational modifications (PTMs) of disease-related proteins, e.g. Tau & alpha-synuclein.

Drug Discovery

Carbohydrates are essential molecules in health and diseases but rarely explored as drug candidates – presumably due to their high polarity and inherently poor pharmacokinetic properties. We develop drug-like, carbohydrate-based molecule by chemically modify the natural carbohydrate scaffolds.

Medicinal Chemistry

Modern drug discovery has been impeded by the lack of structurally or stereochemically complex small molecules in chemical screening libraries. By late-stage chemical modifications of natural products or existing drug molecules, we create complex drug-like molecules with diverse chemical structures and novel mechanisms of action. Using this strategy, we synthesize pseudo-natural products with potent neuroprotective effects that are not observed in the parental natural products.

Programmable PTM editing and induced-proximity chemical biology

1.  “Rewiring c-Myc transcriptional activity with an O-GlcNAcylation targeting chimera (OGTAC)” Xu, T., Guo, Z., Khan, K. S., Huang, Y., Ma, B., Liu, J., Felsher, D. W. & Ng, B.W.-L.^#

Cell Chem. Biol., in revision. Preprint: bioRxiv, https://doi.org/10.64898/2026.05.04.722559 (2026).

2. “Ligand-directed self-assembling chimeras for targeted protein O-GlcNAcylation” Guo, Z., Xu, T., Khan, K., Scheeff, S., Qin, Y., Yu, S.-Y., Lo, R., Li, Y., Xie, Y., Ma, B., Huang, Y., Yan, H., Chung, C.Y.-S., Tamura, T., Hamachi, I. & Ng, B.W.-L.^# ACS Chem. Biol. 20, 2907–2916 (2025).

• This article was ranked among the “Most Read articles” of the journal.

3. “Targeted O-GlcNAcylation of CK2α triggers its ubiquitin-proteasome degradation and alters downstream phosphorylation” Xu, T., Ma, B., Li, Y., Guo, Z., Zhang, M. & Ng, B.W.-L.^# ACS Chem. Biol. 20, 1646–1659 (2025).

• This article was ranked among the “Most Read articles” of the journal.

4. “Targeted protein O-GlcNAcylation using bifunctional small molecules” Ma, B., Khan, K.S., Xu, T., Amada, J.X., Guo, Z., Huang, Y., Yan, Y., Lam, H., Cheng, A.S.-L. & Ng, B.W.-L.^# J. Am. Chem. Soc. 146, 9779–9789 (2024).

• Press release: CUHK discovers groundbreaking method for precise regulation of human proteins Paving the way for the development of new drugs for numerous diseases

Natural product molecular editing and therapeutic scaffold discovery 

5. “Molecular editing of bilobalide: regioselective C-ring lactam formation” Wang, W., Scheeff, S., Hau, S. C.-K., Qin, Y., Sillapachaiyaporn, C. & Ng, B.W.-L.^# Org Lett ASAP (2026).

6. “Lactone-to-lactam editing alters the pharmacology of bilobalide” Jiang, X., He, X., Wong, J., Scheeff, S., Hau, S.C.K., Wong, T. H., Qin, Y., Fan, C. H., Ma, B., Chung, N. L., Huang, J., Zhao, J., Yan, Y., Xiao, M., Song, X., Hui, T., Zuo, Z., Wu, W.K.K., Ko, H., Chow, K. H.-M. & Ng, B.W.-L.^# JACS Au 4, 3537–3546 (2024).

• This article was featured as a cover art (supplementary).
• Press release: CU Medicine modifies Gingko tree extract with innovative molecular editing
• This article was highlighted in Synfacts, 2024, 20, 1091. 

7. “Palladium-catalyzed arylation of carbasugars enables the discovery of potent and selective SGLT2 inhibitors” Ng, W.-L., Lau, K. M., Lau, C. B. & Shing, T. K. M. Angew Chem Int Ed 55, 13818–13821 (2016).

• This article was highlighted in Synfacts, 2017, 13, 17.
• Press release: CUHK Scientists Successfully Synthesize New Carbasugars as Antidiabetic Agents

 Antiviral medicinal chemistry and noncanonical nucleoside scaffolds

8. “Antiviral profiling and cellular activation of carbobicyclic nucleoside analogues” Scheeff, S., Baguio, J.M.J., Liang, B.Z., Amada, J.X., Tao, K.P., De Jonghe, S., Persoons, L., Chow, T.H.-Y., Tse, C.K.M., Wu, R.Y., Xu, X., Zuo, Z., Cheung, P.P.-H., Chan, R.W.Y. & Ng, B.W.-L.^# Journal of Medicinal Chemistry 69, 5501–5539 (2026).

• Press release: CUHK develops a novel antiviral molecular scaffold, enabling safer and more efficient antiviral drug design against viral mutations

9. “Design and synthesis of bicyclo[4.3.0]nonene nucleoside analogues” Scheeff, S., Wang, Y., Lyu, M.-Y., Ahmadabadi, B.N., Hau, S.C.K., Hui, T.K.C., Zhang, Y., Zuo, Z., Chan, R.W.Y.^# & Ng, B.W.-L.^# Org Lett 25, 9002–9007 (2023).

10. “Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir” Lo, H. S., Hui, K. P. Y., Lai, H.-M., He, X., Khan, K. S., Kaur, S., Huang, J., Li, Z., Chan, A. K. N., Cheung, H. H.-Y., Ng, K.-C., Ho, J. C. W., Chen, Y. W., Ma, B., Cheung, P. M.-H., Shin, D., Wang, K., Lee, M.-H., Selisko, B., Eydoux, C., Guillemot, J.-C., Canard, B., Wu, K.-P., Liang, P.-H., Dikic, I., Zuo, Z., Chan, F. K. L., Hui, D. S. C., Mok, V. C. T., Wong, K.-B., Mok, C. K. P., Ko, H., Aik, W. S., Chan, M. C. W.^# & Ng, W.-L.^# ACS Cent Sci 7, 792–802 (2021).

• This article was selected as part of “Examples of the Exceptional, COVID19 Special Collection” of ACS Cent Sci.
• Press release: A Global Study Led by CU Medicine and HKUMed Discovers a Hepatitis C Virus Drug as Potent Treatment for COVID-19

11. “Coronavirus RNA proofreading: molecular basis and therapeutic targeting” Robson, F., Khan, K.S., Le, T.K., Paris, C., Demirbag, S., Barfuss, P., Rocchi, P., Ng, W.-L.^# Molecular Cell 79, 710–727 (2020).

• This article was recognized as a “Highly Cited Paper” by Clarivate Web of Science (Top 1% in Molecular Biology & Genetics). It was also highlighted by The Scientist, 2021, July issue.

(# Denotes corresponding author)