Drug Discovery Core of the FAMRI Center of Excellence
Leadership
Director: Jun O. Liu, PhD (2018–present)
Co-Director: Ronald Schnaar (2018–present)
Manager: Alan Long (2018-present)
To learn about our capabilities and start a project, contact core manager Alan Long.
Former Directors:
Philip Cole, M.D., Ph.D., and Julie Brahmer, M.D. (2013–2018)
Charles Rudin, M.D., Ph.D. (2005–2013)
Core Location:
Johns Hopkins East Baltimore Campus
Miller Research Building, Room 346
733 N Broadway, Baltimore, MD
What We Provide
Our core provides critical resources for drug screening and early-stage drug discovery by facilitating broad chemical space exploration and the use of commercial drug libraries and those that have been exclusively developed by Johns Hopkins researchers over the past decade.
Compound Libraries:
The Johns Hopkins Drug Library
- 4,700 existing drugs that have been approved by the US FDA or its foreign counterparts for human use.
- First-of-its-kind established in an academic institution and has helped catalyze the field of drug repurposing across academia and pharmaceutical companies.
- Key advantage: hits from screens with sufficient potency can be rapidly translated into human clinical studies, greatly accelerating the drug discovery process.
Molecular Glue Rapafucin Library
- 45,000 compounds in the hybrid macrocycle (rapafucin) molecular glue library.
- Inspired by the natural product-derived drug rapamycin.
- Rapafucins retain the FKBP-binding domain of rapamycin but contain an oligopeptide domain in place of the mTOR-interacting effector domain of rapamycin. Upon binding to FKBP, the resultant FKBP-rapafucin complexes form a neosurface with areas comparable to antibodies, allowing them to disrupt or modulate protein-protein interactions and to conquer undruggable targets.
ChemDiv Library
- The commercial ChemDiv diversity small molecule library is available in two different versions, 10K and 100K, for pilot and full-scale screens.
Core Services
Experts in the core support all levels of drug screening services, from assay design through preliminary data analysis.
- High throughput screening of small-molecule libraries including biochemistry and cell-based assays
- Assay development and implementation customized to investigator research goals
- Pilot/proof-of-concept screening using smaller, focused libraries
- Preliminary data analysis and hit picking
- Process automation services, including single cell sequencing support, MODLI-TOF workflows and large-scale sample preparation and reformatting
Impact and Notable Achievements
Research conducted through the core has contributed to discoveries, including:
- Identification of itraconazole as a novel inhibitor of angiogenesis and Hedgehog signaling
- Identification of a stereoisomer of itraconazole as a more potent and less toxic anti-angiogenic drug candidate for non-small cell lung cancer
- Repurposing of nitroxoline as an anticancer agent now in a Phase 3 clinical trial
- Development of the molecular glue rapafucin library and discovery of a highly potent and isoform-specific ENT1 inhibitor that is in late preclinical development as a first-in-class treatment of acute kidney injury
Publications, Inventions, Pipelines and Companies
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Inventions Disclosed to Johns Hopkins Technology Ventures
C11009
Lysosomal Cholesterol Trafficking Pathway as a New Target for Inhibition of Angiogenesis
Yongjun Dang, Jun Liu, Jing Xu
Flight Attendant Medical Research Institute (FAMRI)C11318
Nelfinavir as a Her2-positive Breast Cancer and a Novel Hsp90 Inhibitor
Jun Liu, Joong Sup Shim
Flight Attendant Medical Research Institute (FAMRI)C11500
Itraconazole Stereoisomers and Use Thereof
Shridhar Bhat, Jun Liu, Benjamin Nacev, Wei Shi
Flight Attendant Medical Research Institute (FAMRI)C12754
New Drug Combinations For the Treatment of Breast Cancer
Paweena Chalugun, Jun Liu, Joong Sup Shim
Flight Attendant Medical Research Institute (FAMRI)C13502
Screening Strategy Resulting in Off-label Use of Statins to Target Cells with Cancer Causing Mutations
Huaqing Cai, Alexandra Debonnes, Peter Devreotes, Marc Edwards, Thomas Lampert, Jun Liu, Yu Long, Michele Vitolo
Flight Attendant Medical Research Institute (FAMRI)C15295
Phosphomimetics-containing Rapafucins and Use Thereof
Venkata Subbarao Ayinampudi, Jun Liu, Yuefan Wang, Zhong-Yin Zhang
Flight Attendant Medical Research Institute (FAMRI)C15634
Non-immunosuppressive FK506 analogs and use thereof
Ali Ahmadi, Zufeng Guo, Jun Liu, Brandon Peiffer, Hanjing Peng, Le Qi, Zhaoli Sun, Yuefan Wang
Flight Attendant Medical Research Institute (FAMRI)C15941
Three-dimentional Surface for Protein and Small Molecule Microarrays
Zhiqiang Cheng, Zufeng Guo, Jun Liu, Hanjing Peng, Heng Zhu
Flight Attendant Medical Research Institute (FAMRI)C16068
Glutriptolides--preparation and use thereof
Emmanuel Datan, Jun Liu, Il Minn, Martin Pomper, Peng Xu, Biao Yu
Flight Attendant Medical Research Institute (FAMRI)C17389
Rapaprotin and Analogs and Use Thereof
Venkata Subbarao Ayinampudi, Christian Gocke, Zufeng Guo, Sam Hong, Jun Liu, William Matsui, Hanjing Peng, Brett Ullman
Flight Attendant Medical Research Institute (FAMRI)C18007
Inhibitors of PIN1 and Use Thereof
Jun Liu, Zhongnan Ma
Flight Attendant Medical Research Institute (FAMRI)C18952
Novel Glucose Transporter Inhibitors with Improved Properties and Use Thereof
Venkata Subbarao Ayinampudi, Sage Cho, Marnie Kotlyar, Jun Liu, Zhaoli Sun
Flight Attendant Medical Research Institute (FAMRI)C18953
Synthetic Superstolides and Therapeutic Use Thereof
Catherine Chen, Ruth Hartke, Zhendong Jin, Jun Liu, Shan Qian, Haibo Qiu, Phillip Sanchez, Miao Xu, Wei Zheng
Flight Attendant Medical Research Institute (FAMRI)C19025
Macrocyclic Peptides Bind to the HIF-1alpha Transactivation Domain to Inhibit p300 Binding, HIF-1 target Gene Expression, and Tumor Growth
Venkata Subbarao Ayinampudi, Emmanuel Datan, Jun Liu, Gregg Semenza
Flight Attendant Medical Research Institute (FAMRI)C19316
Molecular glue inhibitors of STAT3 and use thereof
Venkata Subbarao Ayinampudi, Jun Liu, Zhongnan Ma
Flight Attendant Medical Research Institute (FAMRI) -
Nitroxoline
- Development stage: Phase 3
- Indication: non-muscle invasive bladder cancer
Itraconazole
- Development stage: Phase 2
- Indication: Basal cell carcinoma, prostate cancer, lung cancer
Itraconazole Stereoisomer C
- Development stage: Phase 1/2
- Indication: non-small cell lung cancer
Rapadocin
- Development stage: Preclinical-IND enabling
- Indication: acute kidney injury
Rapaglutins
- Development stage: Preclinical
- Indication: cancer and autoimmune diseases
Rapaprotin
- Development stage: Preclinical
- Indication: multiple myeloma and other cancers
Rapastatin
- Development stage: Preclinical
- Indication: cancer and inflammation
Rapireon (IRE1 activator)
- Development stage: Preclinical
- Indication: neurodegeneration
Rapirein (IRE1 inhibitor)
- Development stage: Preclinical
- Indication: cancer and inflammation
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Companies launched using, at least in part, intellectual properties generated at the FAMRI DDC include:
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2010
Xu, J., Dang, Y., Ren, Y. R. and Liu, J. O. (2010) “Cholesterol trafficking is required for mTOR activation in endothelial cells.” Proc. Natl. Acad. Sci. USA, 107, 4764–4769.
Shi, W., Nacev, B. A., Bhat, S. and Liu, J. O. (2010) “Impact of absolute stereochemistry on the antiangiogenic and antifungal activities of itraconazole.” ACS Med. Chem. Lett. 1, 155–159.
Kim, J., Tang, J. Y., Gong, R., Kim, J., Lee, J. J., Clemons, K. V., Chong, C. R., Chang, K. S., Fereshteh, M., Gardner, D., Reya, T., Liu, J. O., Epstein, E. H., Stevens, D. A., Beachy, P. A. (2010) “Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth.” Cancer Cell, 17, 388–399.
Lin J, Haffner MC, Zhang Y, Lee BH, Brennen WN, Britton J, Kachhap SK, Shim JS, Liu JO, Nelson WG, Yegnasubramanian S, Carducci MA. (2010) “Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth.” Prostate 71, 333–343.
Shim, J. S., Matsui, Y., Bhat, S., Nacev, B. A., Xu, J., Bhang, H. E., Dhara, S., Han, K. C., Chong, C. R., Pomper, M. G., So, A. and Liu, J. O. (2010) “Effect of nitroxolibne on angiogenesis and growth of human bladder cancer.” J. Natl. Cancer Inst. 102, 1855–1873.
2011
Wilson, B. A., Wang, H., Nacev, B. A., Mease, R. C., Liu, J. O., Pomper, M. G., and Isaacs, W. B. (2011) “High-throughput screen identifies novel inhibitors of cancer biomarker a-methyacyl coenzyme A racemase (AMACR/P504S).” Mol. Cancer Ther. 10, 825–838.
Platz, E. A., Yegnasubramanian, S., Liu, J. O., Chong, C. R., Shim, J. S., Kenfield, S. A., Stampfer, M. J., Willett, W. C., Giovannucci, E. and Nelson, W. G. (2011) “A novel two-stage, transdisciplinary study identifies digoxin as a possible drug for prostte cancer treatment.” Cancer Discovery. 1, 68–77.
Nacev, B., Low, W. K., Huang, Z., Su, T., Su, Z., Alkuraya, H., Kasuga, D., Sun, W., Trager, M., Braun, M., Fischer, G., Zhang, K., Liu, J. O. (2011) “A calcineurinindependent mechanism of angiogenesis inhibition by a non-immunosuppressive cyclosporin A analog.” J. Pharmacol. Exp. Ther. 338, 466–475.
Shi, W., Nacev. B. A., Aftab, B. T., Rudin, C. M., Liu, J. O. (2011) “Itraconazole side chian analogues: Structure-activity relathionship studies for inhibition of endothelial cell proliferation, vascular endothelial growth factor receptor 2 (VEGF2) glycosylation, and hedgehog signaling” J. Med. Chem. 54, 7363–7374.
Nacev. B. A., Liu, J. O. (2011) “Synergistic inhibition of endothelial cell proliferation, tube formation, and sprouting by cyclosporine A and itraconazole” PLoS One 6, e24793.
Aftab. B. T., Dobromilskaya, I., Liu, J. O., Rudin, C. M. (2011) “Itraconazole inhibits angiogenesis and tumor growth in non-small cell lung cancer” Cancer Res. 71, 6764–6772.
Nacev. B. A., Grassi, P., Dell, A., Haslam, S. M., Liu, J. O. (2011) “The antifungal drug itraconazole inhibits vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, trafficking and signaling in endothelial cells” J. Biol. Chem. 286, 44045–44056.
Rovira, M., Huang, W., Yusuff, S., Shim, J. S., Ferrante, A. A., Liu, J. O., Parsons, M. J. (2011) “Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation” Proc. Natl. Acad. Sci. USA 108, 19264–19269.
2012
Xing, S., Bhat, S., Shroff, N. S., Zhang, H., Lopez, J. A., Margolick, J. B., Liu, J. O., Siliciano, R. F. (2012) “Novel structurally related compounds reactivate latent HIV-1 in a bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation.” J. Antimicrob. Chemother. 67, 398–403.
Bhat, S., Shim, J. S., Zhang, F., Chong, C. R., Liu, J. O. (2012) “Substituted oxines inhibit endothelial cell proliferation and angiogenesis.” Org. Biomol. Chem. 10, 2979–2992.
Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S. J., Anders, R. A., Liu, J. O., Pan, D. (2012) “Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP.” Genes Dev. 26, 1300–1305.
Shim, J. S., Rao, R., Beebe, K., Neckers, L., Han, I., Nahta, R., Liu, J. O. (2012) “Selective inhibition of Her2-positive breast cancer cells by the HIV protease inhibitor nelfinavir” J. Natl. Cancer Inst. 104, 1576–1590.
2013
Kamiyama, H., Rauenzahn, S., Shim, J.S., Karikari, C.A., Feldmann, G., Hua, L., Kamiyama, M., Schuler, F.W., Lin, M.T., Beaty, R.M., Karanam, B., Liang, H., Mullendore, M. E., Mo, G., Hidalgo, M., Jaffee, E., Hruban, R. H., Jinnah, H. A., Roden, R. B., Jimeno, A., Liu, J. O., Maitra, A., Eshleman, J. R. (2013). “Personalized chemotherapy profiling using cancer cell lines from selectable mice.” Clin. Cancer Res. 19, 1139–1146.
Choi, S.M., Kim, Y., Shim, J.S., Park, J.T., Wang, R.H., Leach, S.D., Liu, J.O., Deng, C.X., Ye, Z., and Jang, Y.Y. (2013). “Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells.” Hepatology 57, 2458–2468.
Wissing, M.D., Mendonca, J., Kim, E., Shim, J.S., Kaelber, N.S., Kant, H., Hammers, H., Commes, T., Van Diest, P.J., Liu, J. O., Kachhap, S. K. (2013). “Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells.” Cancer Biol. Ther. 14, 401–410.
Fatokun, A. A., Liu, J. O., Dawson, V. L., and Dawson, T. M. (2013). "Identification through high-throughput screening of 4'-methoxyflavone and 3',4'-dimethoxyflavone as novel neuroprotective inhibitors of parthanatos." Br J Pharmacol. 169, 1263–1278.
Rudin, C. M., Brahmer, J. R., Juergens, R. A., Hann, C. L., Ettinger, D. S., Sebree, R., Smith, R., Aftab, B. T., Huang, P., and Liu, J. O. (2013). "Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer." J Thorac Oncol 8, 619–623.
2014
Wang, M., Shim, J. S., Li, R. J., Dang, Y., He, Q., Das, M., and Liu, J. O. (2014). "Identification of an old antibiotic clofoctol as a novel activator of unfolded protein response pathways and an inhibitor of prostate cancer." Br. J. Pharmacol. 171, 4478–4489.
2015
Shim, J. S., Li, R. J., Lv, J., Head, S. A., Yang, E. J., Liu, J. O. (2015) “Inhibition of angiogenesis by selective estrogen receptor modulators through blockade of cholesterol trafficking rather than estrogen receptor antagonism.” Cancer Lett. 362, 106–115.
He, R., Yu, Z. H., Zhang, R. Y., Wu, L., Gunawan, A. M., Lane, B. S., Shim, J. S., Zeng, L. F., He, Y., Chen, L., Wells, C. D., Liu, J. O., Zhang, Z. Y. (2015) “Exploring the Existing Drug Space for Novel pTyr Mimetic and SHP2 Inhibitors.” ACS Med Chem Lett. 6, 782–786.
Wang, G., Rajpurohit, S. K., Delaspre, F., Walker, S. L., White, D. T., Ceasrine, A., Kuruvilla, R., Li, R. J., Shim, J. S., Liu, J. O., Parsons, M. J., Mumm, J. S. (2015) “First quantitative high-throughput screen in zebrafish identifies novel pathways for -cell mass.” eLife. July 28: 4. doi: 10.7554/eLife.08261. PubMed PMID: 26218223.
Head, S. A., Shi, W., Zhao, L., Gorshkov, K., Pasunooti, K., Chen, Y., Deng, Z., Li, R. J., Shim, J. S., Tan, W., Hartung, T., Zhang, J., Zhao, Y., Colombini, M., Liu, J. O. (2015) “Antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling ais in endothelial cells.” Proc. Natl. Acad. Sci. USA. 112, E7276–7285.
2016
He, Q. L., Minn, I., Wang, Q., Xu, P., Head, S. A., Datan, E., Yu, B., Pomper, M. G., and Liu, J. O. (2016) “Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation.” Angew Chem Int Ed Engl 55, 12035–12039.
Head, S. A., and Liu, J. O. (2016) “Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling.” J Vis Exp 115, doi: 10.3791/54529.
Jouanneau, M., McClary, B., Reyes, J. C., Chen, R., Chen, Y., Plunkett, W., Cheng, X., Milinichik, A. Z., Albone, E. F., Liu, J. O., and Romo, D. (2016) “Derivatization of agelastatin A leading to bioactive analogs and a trifunctional probe.” Bioorg Med Chem Lett 26, 2092–2097.
Li, R. J., Xu, J., Fu, C., Zhang, J., Zheng, Y. G., Jia, H., and Liu, J. O. (2016) "Regulation of mTORC1 by lysosomal calcium and calmodulin." Elife 5, e19360.
Robert, C., Nagaria, P.K., Pawar, N., Adewuyi, A., Gojo, I., Meyers, D.J., Cole, P.A., Rassool, F.V. (2016) Histone deacetylase inhibitors decrease NHEJ both by acetylation of repair factors and trapping of PARP1 at DNA double-strand breaks in chromatin Leukemia Research 45 (2016) 14–23.
Shim, J. S., Li, R. J., Bumpus, N. N., Head, S. A., Kumar Pasunooti, K., Yang, E. J., Lv, J., Shi, W., and Liu, J. O. (2016) “Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole.” Clin Cancer Res 22, 2709–2720.
2017
Boija, A., Bijay Mahat, D., Zare, A., Holmqvist, P.-H., Philge, P., Meyers, D. J., Cole, P.A., Lis, J. T., Sternberg, P., Mannervik, M. (2017) CBP Regulates Promoter Proximal RNA Polymerase II Molecular Cell 68, 491–503.
Goodrich, A.C., Meyers, D.J., Frueh, D.P. (2017) Molecular impact of covalent modifications on nonribosomal peptide synthetase carrier protein communication J. Biol. Chem. 292(24) 10002–10013.
Head, S. A., Shi, W. Q., Yang, E. J., Nacev, B. A., Hong, S. Y., Pasunooti, K. K., Li, R. J., Shim, J. S., and Liu, J. O. (2017) “Simultaneous Targeting of NPC1 and VDAC1 by Itraconazole Leads to Synergistic Inhibition of mTOR Signaling and Angiogenesis.” ACS Chem Biol 12, 174–182.
Kosowicz, J.G., Lee, J., Peiffer, B., Guo, Z., Chen, J., Liao, G., Hayward, S.D., Liu, J.O., and Ambinder, R.F. (2017). “Drug Modulators of B Cell Signaling Pathways and Epstein-Barr Virus Lytic Activation.” J Virol 91, e00747-17.
Lasko, L.M., Jakob, C.G., Edalji, R.P., Qiu, W., Montgomery, D., Digiammarino, E., Hansen, T.M., Risl, R., Frey, R., Manaves, V., Shaw, B., Algire, M., Hessler, P., Lam, L., Uziel, T., Faivre, E., Ferguson, D., Buchanan, F., Martin, R.L., Torrent, M., Chiang, G. G., Karukurichi, K., Langston, J. W., de Vries, P., Van Drie, J.H., McElligott, D., Kesicki, E., Marmorstein, R., Sun, C., Cole, P.A., Rosenberg, S.H., Michaelides, M.R., Lai, A., Bromberg, K.D. (2017) Discovery of a Potent Catalytic p300/CBP Inhibitor that Targets Lineage-Specific Tumors Nature 550, 128–132.
Lyu, J., Yang, E.J., Head, S.A., Ai, N., Zhang, B., Wu, C., Li, R.J., Liu, Y., Yang, C., Dang, Y., Kwon, H.J., Ge, W., Liu, J.O. and Shim, J.S. (2017) “Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth.” Cancer letters 409, 91–103.
McClary, B., Zinshteyn, B., Meyer, M., Jouanneau, M., Pellegrino, S., Yusupova, G., Schuller, A., Reyes, J. C. P., Lu, J., Guo, Z., Ayinde, S., Luo, C., Dang, Y., Romo, D., Yusupov, M., Green, R., and Liu, J. O. (2017) “Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A.” Cell Chem Biol 24, 605–613.
Zucconi, B., Cole, P. A. (2017) Allosteric Regulation of Epigenetic Modifying Enzymes. Curr. Opinion Chem. Biol. 39, 109–115.
2018
Bauer, L., Ferla, S., Head, S. A., Bhat, S., Pasunooti, K. K., Shi, W.Q., Albulescu, L., Liu, J.O., Brancale, A., van Kuppeveld, F.J.M., Strating, J. (2018) “Structure-activity relationship study of itraconazole…” Antiviral research. 156, 55–63.
Bhat, S., Hwang, Y., Gibson, M.D., Morgan, M.T., Taverna, S.D., Zhao, Y., Wolberger, C., Poirier, M.G., Cole, P.A. (2018) Hydrazide Mimics for Protein Lysine Acylation To Assess Nucleosome Dynamics and Deubiquitinase Action. J. Am. Chem. Soc., 140, 9478–9485.
Chu, N., Salguero, A.L., Liu, A.Z., Chen, Z., Dempsey, D.R., Ficarro, S.B., Alexander, W.M., Marto, J.A., Li, Y., Amzel, L.M., Gabelli, S.B., Cole, P.A. (2018) Akt Kinase Activation Mechanisms Revealed Using Protein Semisynthesis. Cell 174, 897–907.
Jiang, W., Zhou, X., Li, Z., Liu, K., Wang, W., Tan, R., Cong, X., Shan, J., Zhan, Y., Cui, Z., Jiang, L., Li, Q., Shen, S., Bai, M., Cheng, Y., Li, B., Tan, M., Ma, D.K., Liu, J.O., and Dang, Y. (2018) “Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin.” Blood 131, 1325–1336.
Jung, E.H., Meyers, D.J., Bosch, J., Casadevall, A. (2018) Novel Antifungal Compounds Discovered in Medicines for Malaria Venture’s Malaria Box. mSphere 3: e00537-17.
Kalin, J., Wu, M., Gomez, A., Song, Y., Das, J., Hayward, D., Adejola, N., Panova, I., Chung, H. J., Kim, E., Roberts, H. J., Roberts, J. M., Prusevich, P., Jeliazkov, J. R., Roy Burman, S.S., Fairall, L., Milano, C., Eroglu, A., Proby, C., Dinkova-Kostova, A. T., Hancock, W. W., Gray, J. J., Bradner, J. E., Valente, S., Mai, A., Anders, N. M., Rudek, M. A., Ryu, B., Schwabe, J. W. R., Mattevi, A., Alani, R. M., Cole, P. A. (2018) Targeting the CoREST Complex with Dual Histone Deacetylase and Demethylase Inhibitors. Nature Communications 9:53.
Lam, C., Ferguson, I.D., Mariano, M.C., Lin, Y.T., Murnane, M., Liu, H., Smith, G.A., Wong, S.W., Taunton, J., Liu, J.O., Mitsiades, C.S., Hann, B.C., Aftab, B.T., Wiita, A.P. (2018) “Repurposing tofacitinib as an anti-myeloma therapeutic…” Haematologica 103, 1218–1228.
Li, Y., Pasunooti, K.K., Li, R.J., Liu, W., Head, S.A., Shi, W.Q, Liu, J.O. (2018) “Novel tetrazole-containing analogs of itraconazole…” J Med Chem 61, 11158–11168.
Lyu, J., Yang, E.J., Head, S.A., Ai, N., Zhang, B., Wu, C., Li, R.J., Liu, Y., Chakravarty, H., Zhang, S., Tam, K.Y., Dang, Y., Kwon, H.J., Ge, W., Liu, J.O., Shim, J.S. (2018) “Astemizole Inhibits mTOR Signaling and Angiogenesis…” Int J Biol Sci 14, 1175–1185.
Michaelides, M.R., Kluge, A., Patane, M., Van Drie, J.H., Wang, C., Hansen, T.M., Risi, R.M., Mantei, R., Hertel, C., Karukurichi, K., Nesterov, A., McElligott, D., de Vries, P., Langston, J.W., Cole, P.A., Marmorstein, R., Liu, H., Lasko, L., Bromberg, K.D., Lai, A., Kesicki, E.A. (2018) Discovery of Spiro Oxazolidinediones as Selective, Orally Bioavailable Inhibitors of p300/CBP Histone Acetyltransferases. ACS Med. Chem. Lett., 9, 28–33.
Wu M., Hayward, D., Kalin, J.H., Song, Y., Schwabe, J.W.R., Cole, P.A. (2018) Lysine-14 acetylation of histone H3 in chromatin confers resistance… eLife 2018; 7:e37231.
2019
Guo, Z., Hong, S.Y., Wang, J., Rehan, S., Liu, W., Peng, H., Das, M., Li, W., Bhat, S., Peiffer, B., Ullman, B.R., Tse, C.M., Tarmakova, Z., Schiene-Fischer, C., Fischer, G., Paarvilainen, V.O., Sun, Z., Liu, J.O. (2019A) “Rapamycin-inspired macrocycles with new target specificity.” Nat Chem 11, 254–263.
Guo, Z., Cheng, Z., Wang, J., Liu, W., Peng, H., Wang, Y., Rao, S., Li, R., Ying, X., Korangath, P., Liberti, M., Li, Y., Xie, Y., Hong, S., Schiene-Fischer, C., Fischer, G., Locasale, J., Sukumar, S., Zhu, H., Liu, J.O. (2019B) “Discovery of a potent GLUT inhibitor using rapafucin 3D microarrays.” Angew Chem Int Ed Engl 58, 17158–17162.
Kim E, Zucconi BE, Wu M, Nocco SE, Meyers DJ, McGee JS, Venkatesh S, Cohen DL, Gonzalez EC, Ryu B, Cole PA, Alani RM (2019) MITF Expression Predicts Therapeutic Vulnerability… Cancer Res;79:2649–2661.
Lee, J., Kosowicz, J.G., Hayward, S.D., Desai, P., Stone, J., Lee, J.M., Liu, J.O., Ambinder, R.F. (2019) “Pharmacologic Activation of Lytic Epstein-Barr Virus Gene Expression…” J. Virol. Epub 2019/07/26. doi: 10.1128/JVI.00998-19.
Meyer, K.J., Meyers, D.J., Shapiro, T.A. (2019) Optimal kinetic exposures… J Antimicrob Chemother; 74: 2303–2310.
Peiffer, B.J., Qi, L., Ahmadi, A.R., Wang, Y., Guo, Z., Peng, H., Sun, Z., Liu, J.O. (2019) “Activation of BMP signaling…” Cell Chem Biol 26, 652–661.
Wang, Y., Peiffer, B.J., Su, Q., Liu, J.O. (2019) “One-step Heck Reaction Generates…” ACS Med Chem Lett 10, 1279–1283.
Zucconi, B. E., Makofske, J. L., Meyers, D. J., Hwang, Y., Wu, M., Kuroda, M.I., Cole, P. A. (2019) “Combination Targeting of the Bromodomain…” Biochemistry 58, 2133.
2020
Kapoor A, Ghosh AK, Forman M, Hu X, Ye W, Southall N, Marugan J, Keyes RF, Smith BC, Meyers DJ, Ferrer M, and Arav-Boger R. (2020) Validation and Characterization… J. Med. Chem., 63(8), 3896–3907.
Datan E, Minn I, Xu P, He QL, Ahn HH, Yu B, Pomper MG, Liu JO. (2020) A Glucose-Triptolide Conjugate… iScience. 23(9):101536.
Li Y, Pasunooti KK, Peng H, Li RJ, Shi WQ, Liu W, Cheng Z, Head SA, Liu JO. (2020) Design and Synthesis… ACS Med Chem Lett. 11(6):1111–1117.
Tong L, Zhao Q, Datan E, Lin GQ, Minn I, Pomper MG, Yu B, Romo D, He QL, Liu JO. (2020) Triptolide: reflections… Nat Prod Rep. doi: 10.1039/d0np00054j.
2021
Gonzalez-Gil A, Li TA, Porell RN, Fernandes SM, Tarbox HE, Lee HS, Aoki K, Tiemeyer M, Kim J, Schnaar RL. (2021) Isolation, identification and characterization… J Allergy Clin Immunol 147:in press.
Lee HS, Gonzalez-Gil A, Drake V, Li TA, Schnaar RL, Kim J. (2021) Induction of the endogenous sialoglycan ligand… Glycobiology 31:in press.
Gonzalez-Gil A, Schnaar RL. (2021) Glycobiology in Inflammation. In: Encyclopedia of Cell Biology, 2nd Edition, edited by Hart GW. Amsterdam: Elsevier Science, in press.
2022
Guo X, Ghosh AK, Miller H, Knox K, Kundu M, Peterson F, Meyers DJ, Arav-Boger R. (2022b) Inhibition of Human Coronaviruses… Infect Dis Diag Treat 6:199.
Guo X, Ghosh AK, Keyes RF, Peterson F, Forman M, Meyers DJ, Arav-Boger R. (2022a) The Synthesis and Anti-Cytomegalovirus Activity… Viruses. 14:234.
Park H, Kam TI, Peng H, Chou SC, Mehrabani-Tabari AA, Song JJ, Yin X, Karuppagounder SS, Umanah GK, Rao AVS, Choi Y, Aggarwal A, Chang S, Kim H, Byun J, Liu JO, Dawson TM, Dawson VL. (2022) PAAN/MIF nuclease inhibition… Cell. 185:1943–1959.e21.
Salman S, Meyers DJ, Wicks EE, Lee SN, Datan E, Thomas AM, Anders NM, Hwang Y, Lyu Y, Yang Y, Jackson W 3rd, Dordai D, Rudek MA, Semenza GL. (2022) HIF inhibitor 32-134D… J Clin Invest. 132:e156774.
2023
Chu J, Yang J, Zhou Y, Chen J, Chen KH, Zhang C, Cheng HY, Koylass N, Liu JO, Guan Y, Qiu Z. (2023) ATP-releasing SWELL1 channel… Sci Adv. 9(13):eade9931.
Fang H, Wang X, Damarla M, Sun R, He Q, Li R, Luo P, Liu JO, Xia Z. (2023) Dimethyl Fumarate Protects… Mediators Inflamm. 2023:5133505.
Gonzalez-Gil A, Li TA, Kim J, Schnaar RL. (2023) Human sialoglycan ligands… Mol Aspects Med. 90:101110.
Qian S, Head SA, Sanchez PR, Liu JO, Jin Z. (2023) Synthesis and biological evaluation… Bioorg Med Chem Lett. 91:129372.
Reyes Gaido OE, Pavlaki N, Granger JM, Mesubi OO, Liu B, Lin BL, Long A, Walker D, Mayourian J, Schole KL, Terrillion CE, Nkashama LJ, Hulsurkar MM, Dorn LE, Ferrero KM, Huganir RL, Muller FU, Wehrens XHT, Liu JO, Luczak ED, Bezzerides VJ, Anderson ME. (2023) An improved reporter identifies ruxolitinib… Sci Transl Med. 15(701):eabq7839.
Sanchez PR, Head SA, Qian S, Qiu H, Roy A, Jin Z, Zheng W, Liu JO. (2023) Modulation of the Endomembrane System… Int J Mol Sci. 24(11).
Schnaar RL. (2023) Gangliosides as Siglec ligands. Glycoconj J. 40(2):159–67.
2024
Qiu, H., Qian, S., Head, S. A., Sanchez, P. R., Liu, J. O. and Jin, Z. (2024) “Insights into the structure-activity relationship of the anticancer compound ZJ-101: A role played by the amide moiety.” Bioorg. Med. Chem. Lett. 105, 129741.
Li, Q., Liu, Y., Wu, J., Zhu, Z., Fan, J., Zhai, L., Wang, Z., Du, G., Zhang, L., Hu, J., Ma, D. K., Liu, J. O., Huang, H., Tan, M., Dang, Y. and Jiang, W. (2024) “P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.” Leukemia 38, 1751–1763.
Li, T. A., Gonzalez-Gil, A., Awol, A. K., Ackerman, S. J., Orsburn, B. C. and Schnaar, R. L. (2024) “Sialylated keratan sulfates on MUC5B are Siglec-8 ligands in the human esophagus.” Glycobiology 34.
Liu, J., He, Q.-L., Zhou, J., Chikarmane, R., Hauk, G., Rachakonda, A. M., Vaghasia, A. M., Castagna, N., Steinberg, R. C. and Pham, M.-T. (2024) “Triptolide sensitizes cancer cells to nucleoside DNA methyltransferase inhibitors through inhibition of DCTPP1-mediated cell-intrinsic resistance.” bioRxiv.
2025
Rao, A. S., Kotlyar, M., Peng, H., Liu, J. O. (2025) “Next-Generation GLUT Inhibitors: Lactone to Lactam Conversion in Rapaglutin A Confers Resistance to Plasma Esterases.” ACS Med. Chem. Lett. 16, 2273-2279.
Kotlyar, M., Guo, Z., Rao, A. V. S., Peng, H., Wang, J., Ma, Z., Schiene-Fischer, C., Fischer, G. and Liu, J. O. (2025) “Identification of Rapaglutin E as an Isoform-Specific Inhibitor of Glucose Transporter 1.” ACS Chem. Biol. 20, 1004–1009.
Peng, H., Guo, Z., Wang, W.L., Yin, D., Zou, S., Asbell, T., Ullman, B.R ., Thakar, M., Zhang, F., Hong, S. Y., Rao, A. V .S., Wang, K., Zhang, S., Wu, Z., Li, X., Kendra, A. A,, Margolis, S. S., Matsui, W. H., Gocke, C. B., Mao, Y., Liu, J. O. (2025) “Rapaprotin is Activated by an Endopeptidase to Disassemble 26S Proteasome.” Angew Chem Int Ed Engl. 2025 Sep 17:e202500288.
Our Equipment
Mission and Brief History
The ChemCore High Throughput and Drug Discovery Core is supported by the Johns Hopkins Kimmel Cancer Center and the Institute for Basic Biomedical Sciences. The core has its roots in the Johns Hopkins FAMRI Center of Excellence, which was founded in 2005 and is dedicated to biomedical discovery and translation related to cigarette smoke–related diseases. The FAMRI Center of Excellence has supported research in four core facilities and a variety of developmental projects that span drug discovery, in vivo animal model analysis, clinical studies and population-based exposures and outcomes.
Projects supported within the core have included studies on telomeres and fibrosis, head and neck cancer therapies, epigenetics of lung cancer, and chemoprotection against asthma. The core has supported research that has led to the discovery of the antifungal drug itraconazole as a novel inhibitor of angiogenesis and the Hedgehog signaling pathway, the repurposing of the antibiotic nitroxoline as a novel anticancer agent for bladder cancer that has entered a phase 3 trial, and the development of a protein–small molecule conjugate for the potential treatment of immune and inflammatory lung diseases.
Support from FAMRI continues today, as part of the Drug Discovery Core and Drug Library Screening Center, led by Dr. Jun Liu. The Drug Library Screening Center also has been supported by the Synthetic Core Facility, led by Dr. David Meyers.