Honors & Awards

  • Global Ph.D. Fellowship, Ministry of Science & ICT, Republic of Korea (2016-2020)
  • ICBS Poster Award, 6th Official Conference of the International Chemical Biology Society (2017)
  • Poster Presentation Award, 118th Annual Meeting of Korean Chemical Society (2016)
  • The National Scholarship for Science and Engineering, Korea Student Aid Foundation, Republic of Korea (2013-2014)

Professional Education

  • Doctor of Philosophy, Seoul National University (2021)
  • Bachelor of Science, Seoul National University (2015)
  • Ph.D., Seoul National University, Chemistry (2021)
  • B.S., Seoul National University, Biological Science (2015)
  • B.S., Seoul National University, Chemistry (2015)

Stanford Advisors

All Publications

  • STING upregulation strategies to potentiate STING immunotherapy. Future medicinal chemistry Cho, W., Lee, J. H., Park, S. B. 2023

    View details for DOI 10.4155/fmc-2023-0227

    View details for PubMedID 37791535

  • Inflachromene attenuates seizure severity in mouse epilepsy models via inhibiting HMGB1 translocation. Acta pharmacologica Sinica Dai, S. J., Shao, Y. Y., Zheng, Y., Sun, J. Y., Li, Z. S., Shi, J. Y., Yan, M. Q., Qiu, X. Y., Xu, C. L., Cho, W. S., Nishibori, M., Yi, S., Park, S. B., Wang, Y., Chen, Z. 2023; 44 (9): 1737-1747


    Epilepsy is not well controlled by current anti-seizure drugs (ASDs). High mobility group box 1 (HMGB1) is a DNA-binding protein in the nucleus regulating transcriptional activity and maintaining chromatin structure and DNA repair. In epileptic brains, HMGB1 is released by activated glia and neurons, interacting with various receptors like Toll-like receptor 4 (TLR4) and downstream glutamatergic NMDA receptor, thus enhancing neural excitability. But there is a lack of small-molecule drugs targeting the HMGB1-related pathways. In this study we evaluated the therapeutic potential of inflachromene (ICM), an HMGB-targeting small-molecule inhibitor, in mouse epilepsy models. Pentylenetetrazol-, kainic acid- and kindling-induced epilepsy models were established in mice. The mice were pre-treated with ICM (3, 10 mg/kg, i.p.). We showed that ICM pretreatment significantly reduced the severity of epileptic seizures in all the three epilepsy models. ICM (10 mg/kg) exerted the most apparent anti-seizure effect in kainic acid-induced epileptic status (SE) model. By immunohistochemical analysis of brain sections from kainic acid-induced SE mice, we found that kainic acid greatly enhanced HMGB1 translocation in the hippocampus, which was attenuated by ICM pretreatment in subregion- and cell type-dependent manners. Notably, in CA1 region, the seizure focus, ICM pretreatment mainly inhibited HMGB1 translocation in microglia. Furthermore, the anti-seizure effect of ICM was related to HMGB1 targeting, as pre-injection of anti-HMGB1 monoclonal antibody (5 mg/kg, i.p.) blocked the seizure-suppressing effect of ICM in kainic acid-induced SE model. In addition, ICM pretreatment significantly alleviated pyramidal neuronal loss and granule cell dispersion in kainic acid-induced SE model. These results demonstrate that ICM is an HMGB-targeting small molecule with anti-seizure potential, which may help develop a potential drug for treating epilepsy.

    View details for DOI 10.1038/s41401-023-01087-6

    View details for PubMedID 37076634

    View details for PubMedCentralID PMC10462729

  • Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy. Angewandte Chemie (International ed. in English) Cho, W., Won, S., Choi, Y., Yi, S., Park, J. B., Park, J. G., Kim, C. E., Narayana, C., Kim, J. H., Yim, J., Choi, Y. I., Lee, D. S., Park, S. B. 2023; 62 (18): e202300978


    Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.

    View details for DOI 10.1002/anie.202300978

    View details for PubMedID 36827625

  • S-Benproperine, an Active Stereoisomer of Benproperine, Suppresses Cancer Migration and Tumor Metastasis by Targeting ARPC2. Pharmaceuticals (Basel, Switzerland) Jang, H. J., Yoon, Y. J., Choi, J., Lee, Y. J., Lee, S., Cho, W., Byun, W. G., Park, S. B., Han, D. C., Kwon, B. M. 2022; 15 (12)


    Metastasis, in which cancer cells migrate to other tissues and form new tumors, is a major cause of both cancer death and treatment failure. In a previous study, benproperine (Benp) was identified as a cancer cell migration inhibitor and an inhibitor of actin-related protein 2/3 complex subunit 2 (ARPC2). However, Benp is a racemic mixture, and which stereoisomer is the active isomer remains unclear. In this study, we found that S-Benp is an active isomer and inhibits the migration and invasion of cancer cells much more strongly than R-Benp, with no effect on normal cells. The metastasis inhibitory effect of S-Benp was also verified in an animal model. Validating that inhibitors bind to their targets in cells and tissues has been a very challenging task in drug discovery. The direct interactions between ARPC2 and S-Benp were verified by surface plasmon resonance analysis (SPR), a cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS). In the mutant study with ARPC2F225A cells, S-Benp did not bind to ARPC2F225A according to CETSA and DARTS. Furthermore, we validated that S-Benp colocalized with ARPC2 in cancer cells and directly bound to ARPC2 in tumor tissues using Cy3-conjugated S-Benp according to CETSA. Finally, actin polymerization assays and immunocytochemistry showed that S-Benp suppressed actin remodeling such as lamellipodium formation. Taken together, our data suggest that S-Benp is an active stereoisomer of Benp and a potential metastasis inhibitor via ARPC2 binding.

    View details for DOI 10.3390/ph15121462

    View details for PubMedID 36558913

    View details for PubMedCentralID PMC9785746

  • Phenotype-based discovery of a HeLa-specific cytotoxic molecule that downregulates HPV-mediated signaling pathways via oxidative damage. Organic & biomolecular chemistry Lee, S., Cho, W., Hong, S., Yi, S., Kim, H., Baek, S. Y., Park, H., Jung, J., Shin, Y. K., Park, S. B. 2019; 17 (31): 7388-7397


    Selective bioactive compounds have emerged as major players in chemical biology for their potential in disrupting diverse biological pathways with minimal adverse effects. Using phenotypic screening, we identified an anti-cancer agent, SB2001, with a highly specific cytotoxicity toward HeLa human cervical cancer cells. The subsequent mechanistic study revealed that SB2001 induced apoptotic cell death through restoring p53 function and suppressed the human papillomavirus (HPV)-mediated oncoprotein signaling pathway via oxidative damage in HeLa cells. SB2001 also selectively induced HeLa-specific tumor regression without any adverse effects in an in vivo tumor xenograft model, demonstrating its potential as a promising chemical probe.

    View details for DOI 10.1039/c9ob01341e

    View details for PubMedID 31342041

  • Monochromophoric Design Strategy for Tetrazine-Based Colorful Bioorthogonal Probes with a Single Fluorescent Core Skeleton. Journal of the American Chemical Society Lee, Y., Cho, W., Sung, J., Kim, E., Park, S. B. 2018; 140 (3): 974-983


    Fluorogenic bioorthogonal probes are ideal for fluorescent imaging in live cell conditions. By taking advantage of the dual functionality of tetrazine (Tz), as a bioorthogonal reaction unit as well as a fluorescence quencher, a fluorophore-Tz conjugate (FLTz) has been utilized for fluorescent live cell imaging via inverse electron-demand Diels-Alder (iEDDA) type bioorthogonal reactions. However, most FLTz strategies rely on a donor-acceptor-type energy transfer mechanism, which limits red-shifting of probes' emission wavelength without deterioration of the fluorescent turn-on/off ratio. To address this constraint, herein we present a monochromophoric design strategy for making a series of FLTzs spanning a broad range of emission colors. For the systematic comparison of design strategies with minimized structural differences, we selected indolizine-based emission-tunable Seoul-Fluor (SF) as a model fluorophore system. As a result, by inducing strong electronic coupling between Tz and π-conjugation systems of an indolizine core, we efficiently quench the fluorescence of SF-tetrazine conjugates (SFTzs) and achieved more than 1000-fold enhancement in fluorescence after iEDDA reaction with trans-cyclooctene (TCO). Importantly, we were able to develop a series of colorful SFTzs with a similar turn-on/off ratio regardless of their emission wavelength. The applicability as bioorthogonal probes was demonstrated with fluorescence bioimaging of innate microtubule and mitochondria using docetaxel-TCO and triphenylphosphonium-TCO in live cells without washing steps. We believe this study could provide new insight for the reliable and generally applicable molecular design strategy to develop bioorthogonal fluorogenic probes having an excellent turn-on ratio, regardless of their emission wavelength.

    View details for DOI 10.1021/jacs.7b10433

    View details for PubMedID 29240995

  • Synthesis of 3,5-Disubstituted Isoxazoles Containing Privileged Substructures with a Diverse Display of Polar Surface Area. ACS combinatorial science Kim, M., Hwang, Y. S., Cho, W., Park, S. B. 2017; 19 (6): 407-413


    We designed and synthesized the molecular framework of 3,5-disubstituted isoxazoles containing privileged substructures with various substituents which uniquely display polar surface area in a diverse manner. A library of 3,5-disubstituted isoxazoles were systematically prepared via 1,3-dipolar cycloaddition of alkynes with nitrile oxides prepared by two complementary synthetic routes; method A utilized a halogenating agent with a base and method B utilized a hypervalent iodine reagent. Through the biological evaluation of corresponding isoxazoles via three independent phenotypic assays, the different pattern of biological activities was shown according to the type of privileged substructure and substituent. These results demonstrated the significance of molecular design via introducing privileged substructures and various substituents to make a diverse arrangement of polar surface area within a similar 3-dimensional molecular framework.

    View details for DOI 10.1021/acscombsci.7b00032

    View details for PubMedID 28306232

  • Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1-Regulating Anti-inflammatory Agents. Journal of medicinal chemistry Cho, W., Koo, J. Y., Park, Y., Oh, K., Lee, S., Song, J. S., Bae, M. A., Lim, D., Lee, D. S., Park, S. B. 2017; 60 (1): 170-179


    Sepsis is one of the major causes of death worldwide when associated with multiple organ failure. However, there is a critical lack of adequate sepsis therapies because of its diverse patterns of pathogenesis. The pro-inflammatory cytokine cascade mediates sepsis pathogenesis, and high mobility group box proteins (HMGBs) play an important role as late-stage cytokines. We previously reported the small-molecule modulator, inflachromene (1d), which inhibits the release of HMGBs and, thereby, reduces the production of pro-inflammatory cytokines. In this context, we intraperitoneally administered 1d to a cecal ligation and puncture (CLP)-induced mouse model of sepsis and confirmed that it successfully ameliorated sepsis pathogenesis. On the basis of a structure-activity relationship study, we discovered new candidate compounds, 2j and 2l, with improved therapeutic efficacy in vivo. Therefore, our study clearly demonstrates that the regulation of HMGB1 release using small molecules is a promising strategy for the treatment of sepsis.

    View details for DOI 10.1021/acs.jmedchem.6b00954

    View details for PubMedID 28001381

  • Diversity-oriented synthetic strategy for developing a chemical modulator of protein-protein interaction. Nature communications Kim, J., Jung, J., Koo, J., Cho, W., Lee, W. S., Kim, C., Park, W., Park, S. B. 2016; 7: 13196


    Diversity-oriented synthesis (DOS) can provide a collection of diverse and complex drug-like small molecules, which is critical in the development of new chemical probes for biological research of undruggable targets. However, the design and synthesis of small-molecule libraries with improved biological relevance as well as maximized molecular diversity represent a key challenge. Herein, we employ functional group-pairing strategy for the DOS of a chemical library containing privileged substructures, pyrimidodiazepine or pyrimidine moieties, as chemical navigators towards unexplored bioactive chemical space. To validate the utility of this DOS library, we identify a new small-molecule inhibitor of leucyl-tRNA synthetase-RagD protein-protein interaction, which regulates the amino acid-dependent activation of mechanistic target of rapamycin complex 1 signalling pathway. This work highlights that privileged substructure-based DOS strategy can be a powerful research tool for the construction of drug-like compounds to address challenging biological targets.

    View details for DOI 10.1038/ncomms13196

    View details for PubMedID 27774980

    View details for PubMedCentralID PMC5078997

  • A novel small-molecule agonist of PPAR-γ potentiates an anti-inflammatory M2 glial phenotype. Neuropharmacology Song, G. J., Nam, Y., Jo, M., Jung, M., Koo, J. Y., Cho, W., Koh, M., Park, S. B., Suk, K. 2016; 109: 159-169


    Neuroinflammation is a key process for many neurodegenerative diseases. Activated microglia and astrocytes play an essential role in neuroinflammation by producing nitric oxide (NO), inflammatory cytokines, chemokines, and neurotoxins. Therefore, targeting glia-mediated neuroinflammation using small-molecules is a potential therapeutic strategy. In this study, we performed a phenotypic screen using microglia cell-based assay to identify a hit compound containing N-carbamoylated urethane moiety (SNU-BP), which inhibits lipopolysaccharide (LPS)-induced NO production in microglia. SNU-BP inhibited pro-inflammatory cytokines and inducible nitric oxide synthase in LPS-stimulated microglia, and potentiated interleukin-4-induced arginase-1 expression. PPAR-γ was identified as a molecular target of SNU-BP. The PPAR response element reporter assay revealed that SNU-BP specifically activated PPAR-γ, but not PPAR-δ or -α, confirming that PPAR-γ is the target protein of SNU-BP. The anti-inflammatory effect of SNU-BP was attenuated by genetic and pharmacological inhibition of PPAR-γ. In addition, SNU-BP induced an anti-inflammatory phenotype in astrocytes as well, by inhibiting pro-inflammatory NO and TNF-α, while increasing anti-inflammatory genes, such as arginase-1 and Ym-1. Finally, SNU-BP exhibited an anti-inflammatory effect in the LPS-injected mouse brain, demonstrating a protective potential for neuroinflammatory diseases.

    View details for DOI 10.1016/j.neuropharm.2016.06.009

    View details for PubMedID 27288982

  • BOIMPY: Fluorescent Boron Complexes with Tunable and Environment-Responsive Light-Emitting Properties Chemistry - A European Journal Lee, B., Park, B., Cho, W., Lee, H., Olasz, A., Chen, C., Park, S., Lee, D. 2016; 22 (48): 17321-17328

    View details for DOI 10.1002/chem.201603837