Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity
Abstract
Wogonin is a natural product isolated from the Scutellaria baicalensis and has been proved to be a potent and selective inhibitor of CDK9. Using this scaffold, we designed and synthesized a series of proteolysis targeting chimeras (PROTACs) targeting CDK9 by recruiting ubiquitin E3 ligase cereblon (CRBN). For constructing diverse Wogonin-based PROTACs, a "click chemistry" approach was employed for the synthesis of CDK9-targeting PROTACs. The results of western blotting assays showed that compounds containing triazole group in the linker could selectively downregulate the intracellular CDK9 level. Among these compounds, 11c could selectively degrade CDK9 in a concentration-dependent manner. In addition, the application of the proteasome inhibitor MG132 and CRBN siRNA silencing confirmed that 11c could promote the proteasome-dependent and CRBN-dependent degradation. Consistent with the degradation of the CDK9 protein, 11c selectively inhibits proliferation of CDK9-overexpressed cancer cells. Thus, our Wogonin-based PROTAC would be an efficient probe that induces the degradation of CDK9.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
STAT3 protein degradation can be achieved more efficiently and sustainably than technologies that use STAT3 mRNA.
“First, STAT3 protein degradation can be achieved more efficiently and sustainably than technologies that use STAT3 mRNA with the characteristic of rapid degradation (50, 51).”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [51]
Cites
Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760 · see citing works
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486 · see citing works
Small‐Molecule PROTACS: New Approaches to Protein Degradation
Toure, M., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507978 · Cited by 674 · see citing works
Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation
Olson, C. M., Jiang, B., Erb, M. A., Liang, Y., Doctor, Z. M., Zhang, Z., Zhang, T., Kwiatkowski, N., Boukhali, M., Green, J. L., et al. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2538 · Cited by 552 · see citing works
Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC)
Robb, C. M., Contreras, J. I., Kour, S., Taylor, M., Abid, M., Sonawane, Y. A., Zahid, M., Murry, D. J., Natarajan, A., & Rana, S. (2017) · Chemical Communications · doi:10.1039/c7cc03879h · Cited by 221 · see citing works
Dysregulation of the basal RNA polymerase transcription apparatus in cancer
Bywater, M. J., Pearson, R. B., McArthur, G. A., & Hannan, R. D. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3496 · Cited by 219 · see citing works
Lücking, U., Scholz, A., Lienau, P., Siemeister, G., Kosemund, D., Bohlmann, R., Briem, H., Terebesi, I., Meyer, K., Prelle, K., et al. (2017) · ChemMedChem · doi:10.1002/cmdc.201700447 · Cited by 195 · see citing works
Polier, G., Ding, J., Konkimalla, V. B., Eick, D., Ribeiro, N., Köhler, R., Giaisi, M., Efferth, T., Désaubry, L., Krammer, P. H., et al. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.66 · Cited by 168 · see citing works
Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy
Sonawane, Y. A., Taylor, M., Napoleon, J. V., Rana, S., Contreras, J. I., & Natarajan, A. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00150 · Cited by 164 · see citing works
Shao, H., Shi, S., Huang, S., Hole, A. J., Abbas, A. Y., Baumli, S., Liu, X., Lam, F., Foley, D., Fischer, P. M., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301475f · Cited by 130 · see citing works
Zeidner, J. F., Foster, M. C., Blackford, A. L., Litzow, M. R., Morris, L. E., Strickland, S. A., Lancet, J. E., Bose, P., Levy, M. Y., Tibes, R., et al. (2015) · Haematologica · doi:10.3324/haematol.2015.125849 · Cited by 105 · see citing works
A Novel CDK9 Inhibitor Shows Potent Antitumor Efficacy in Preclinical Hematologic Tumor Models
Yin, T., Lallena, M. J., Kreklau, E. L., Fales, K. R., Carballares, S., Torrres, R., Wishart, G. N., Ajamie, R. T., Cronier, D. M., Iversen, P. W., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0849 · Cited by 104 · see citing works
Ding, J., Polier, G., Köhler, R., Giaisi, M., Krammer, P. H., & Li‐Weber, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.286526 · Cited by 85 · see citing works
Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy
Ohoka, N., Shibata, N., Hattori, T., & Naito, M. (2016) · Current Cancer Drug Targets · doi:10.2174/1568009616666151112122502 · Cited by 55 · see citing works
Falco, G. D., Bellan, C., D’Amuri, A., Angeloni, G., Leucci, E., Giordano, A., & Leoncini, L. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.3.1497 · Cited by 50 · see citing works
Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition
Madak, J. T., Cuthbertson, C. R., Chen, W., Showalter, H. D., & Neamati, N. (2017) · Chemistry - A European Journal · doi:10.1002/chem.201702999 · Cited by 38 · see citing works
Cho, S., Kim, Y.-J., Surh, Y., Kim, B. M., & Lee, S. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.209551 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview
Bozorov, K. A., Zhao, J., & Aisa, H. A. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.07.005 · Cited by 871 · see citing works
PROteolysis TArgeting Chimeras (PROTACs) — Past, present and future
Pettersson, M., & Crews, C. M. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2019.01.002 · Cited by 818 · see citing works
PROTACs: great opportunities for academia and industry
Sun, X., Gao, H., Yang, Y., He, M., Wu, Y., Song, Y.-G., Tong, Y., & Rao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0101-6 · Cited by 651 · see citing works
Targeted protein degradation: elements of PROTAC design
Paiva, S.-L., & Crews, C. M. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.02.022 · Cited by 586 · see citing works
Current strategies for the design of PROTAC linkers: a critical review
Troup, R. I., Fallan, C., & Baud, M. G. J. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00018 · Cited by 424 · see citing works
Cell cycle on the crossroad of tumorigenesis and cancer therapy
Liu, J., Peng, Y., & Wei, W. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.07.001 · Cited by 381 · see citing works
Proteolysis-targeting chimeras (PROTACs) in cancer therapy
Li, X., Pu, W., Zheng, Q., Ai, M., Chen, S., & Peng, Y. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01434-3 · Cited by 374 · see citing works
Degradation of proteins by PROTACs and other strategies
Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335 · see citing works
Self-citationThe PROTAC technology in drug development
Zou, Y., Ma, D., & Wang, Y. (2019) · Cell Biochemistry and Function · doi:10.1002/cbf.3369 · Cited by 307 · see citing works
Self-citationZeng, S., Huang, W., Zheng, X., Cheng, L., Zhang, Z., Wang, J., & Shen, Z. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112981 · Cited by 262 · see citing works
Self-citationCyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015–2019)
Sánchez-Martínez, C., Lallena, M. J., Sanfeliciano, S. G., & de Dios, A. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.126637 · Cited by 200 · see citing works
PROTACs: A novel strategy for cancer therapy
Liu, J., Ma, J., Liu, Y., Xia, J., Li, Y., Wang, Z. P., & Wei, W. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.02.006 · Cited by 186 · see citing works
Self-citationE3 ligase ligand chemistries: from building blocks to protein degraders
Sosič, I., Bricelj, A., & Steinebach, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00148a · Cited by 173 · see citing works
Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta
Bai, N., Miller, S. A., Andrianov, G. V., Yates, M., Kirubakaran, P., & Karanicolas, J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01451 · Cited by 157 · see citing works
Developments of CRBN-based PROTACs as potential therapeutic agents
Wang, C., Zhang, Y., Wu, Y., & Xing, D. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113749 · Cited by 152 · see citing works
Wogonin and its analogs for the prevention and treatment of cancer: A systematic review
Banik, K., Khatoon, E., Harsha, C., Rana, V., Dey, P., Thakur, K. K., Bishayee, A., & Kunnumakkara, A. B. (2022) · Phytotherapy Research · doi:10.1002/ptr.7386 · Cited by 151 · see citing works
Characteristic roadmap of linker governs the rational design of PROTACs
Dong, Y., Ma, T., Xu, T., Feng, Z., Li, Y., Song, L., Yao, X., Ashby, C. R., & Hao, G.-F. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.04.007 · Cited by 146 · see citing works
Self-citationRecent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update
Wu, T., Qin, Z., Tian, Y., Wang, J., Xu, C., Li, Z., & Bian, J. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00744 · Cited by 120 · see citing works
Self-citationBivalent Ligands for Protein Degradation in Drug Discovery
Scheepstra, M., Hekking, K. F. W., Hijfte, L. V., & Folmer, R. H. A. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.01.006 · Cited by 120 · see citing works
Strategies for designing proteolysis targeting chimaeras (PROTACs)
He, S., Dong, G., Cheng, J., Wu, Y., & Sheng, C. (2022) · Medicinal Research Reviews · doi:10.1002/med.21877 · Cited by 118 · see citing works
Qiu, X., Li, Y., Yu, B., Ren, J., Huang, H., Wang, M., Ding, H., Li, Z., Wang, J., & Bian, J. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113091 · Cited by 117 · see citing works
Self-citationPROTAC’ing oncoproteins: targeted protein degradation for cancer therapy
Kelm, J. M., Pandey, D. S., Malin, E., Kansou, H. W., Arora, S., Kumar, R., & Gavande, N. S. (2023) · Molecular Cancer · doi:10.1186/s12943-022-01707-5 · Cited by 115 · see citing works
Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action
Łukasik, P., Baranowska‐Bosiacka, I., Kulczycka, K., & Gutowska, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062806 · Cited by 101 · see citing works
Cao, C.-G., Yang, J., Chen, Y. X., Zhou, P., Wang, Y., Du, W., Zhao, L., & Chen, Y. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00821 · Cited by 90 · see citing works
Self-citationProteolysis targeting chimeras (PROTACs) in cancer therapy
Ocaña, A., & Pandiella, A. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01672-1 · Cited by 87 · see citing works
PROTAC: A promising technology for cancer treatment
Zhou, X., Dong, R., Zhang, J., Zheng, X. X., & Sun, L. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112539 · Cited by 84 · see citing works
Development of selective small molecule MDM2 degraders based on nutlin
Wang, B., Wu, S., Liu, J., Yang, K., Xie, H., & Tang, W. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.046 · Cited by 77 · see citing works
Advancing Strategies for Proteolysis-Targeting Chimera Design
Li, M., Zhi, Y., Liu, B., & Yao, Q. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01555 · Cited by 76 · see citing works
Antiviral PROTACs: Opportunity borne with challenge
Liang, J., Wu, Y., Lan, K., Dong, C., Wu, S., Li, S., & Zhou, H. (2023) · Cell Insight · doi:10.1016/j.cellin.2023.100092 · Cited by 74 · see citing works
Wei, D., Wang, H., Zeng, Q., Wang, W., Hao, B., Feng, X., Wang, P., Song, N., Kan, W., Huang, G., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01350 · Cited by 71 · see citing works
Novel approaches for the rational design of PROTAC linkers
Zagidullin, A. A., Milyukov, V. A., Rizvanov, A. A., & Bulatov, E. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00023 · Cited by 70 · see citing works
The Renaissance of Cyclin Dependent Kinase Inhibitors
Ettl, T., Schulz, D., & Bauer, R. J. (2022) · Cancers · doi:10.3390/cancers14020293 · Cited by 71 · see citing works
A novel strategy to block mitotic progression for targeted therapy
Chi, J. J., Li, H., Zhou, Z., Izquierdo-Ferrer, J., Xue, Y., Wavelet, C. M., Schiltz, G. E., Zhang, B., Cristofanilli, M., Lu, X., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.10.013 · Cited by 68 · see citing works
A minireview of 1,2,3‐triazole hybrids with O‐heterocycles as leads in medicinal chemistry
Saroha, B., Kumar, G., Kumar, R., Kumari, M., & Kumar, S. (2021) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13966 · Cited by 66 · see citing works
Pereira, D., Pinto, M. M. M., Correia‐da‐Silva, M., & Cidade, H. M. (2021) · Molecules · doi:10.3390/molecules27010230 · Cited by 66 · see citing works
Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax
King, H. M., Rana, S., Kubica, S. P., Mallareddy, J. R., Kizhake, S., Ezell, E. L., Zahid, M., Naldrett, M. J., Alvarez, S., Law, H. C.-H., et al. (2021) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2021.128061 · Cited by 60 · see citing works
Xiao, L., Liu, Y., Chen, H., & Shen, L. (2023) · Cancer Biology & Therapy · doi:10.1080/15384047.2023.2219470 · Cited by 59 · see citing works
Jin, J., Wu, Y., Zhao, Z., Wu, Y., Zhou, Y.-D., Liu, S., Sun, Q., Yang, G., Lin, J., Nagle, D. G., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.160606 · Cited by 57 · see citing works
“First, STAT3 protein degradation can be achieved more efficiently and sustainably than technologies that use STAT3 mRNA with the characteristic of rapid degradation (50, 51).”
Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation
Xi, M., Chen, Y., Yang, H., Xu, H., Du, K., Wu, C., Xu, Y., Deng, L., Luo, X., Yu, L., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.04.036 · Cited by 56 · see citing works
Targeting Protein Kinases Degradation by PROTACs
Yu, F., Cai, M., Shao, L., & Zhang, J. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.679120 · Cited by 54 · see citing works
Drug discovery inspired by bioactive small molecules from nature
Kim, S., Lim, S.-W., & Choi, J. (2022) · Animal Cells and Systems · doi:10.1080/19768354.2022.2157480 · Cited by 54 · see citing works
Targeting cyclin-dependent kinase 9 in cancer therapy
Shen, Y., Wang, Y., Zhang, Y., Ma, S.-J., Yang, L., Zhao, C., & Huang, X. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00796-0 · Cited by 52 · see citing works
Self-citationMarak, B. N., Dowarah, J., Khiangte, L., & Singh, V. P. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112571 · Cited by 52 · see citing works
Danishuddin, M., Jamal, M. S., Song, K. S., Lee, K., Kim, J.-J., & Park, Y. (2023) · Pharmaceuticals · doi:10.3390/ph16121649 · Cited by 50 · see citing works
Triazol: A Privileged Scaffold for Proteolysis Targeting Chimeras
Xia, L., Ba, M.-Y., Liu, W., Cheng, W., Hu, C.-P., Zhao, Q., Yao, Y., Sun, M., & Duan, Y. (2019) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0159 · Cited by 50 · see citing works
Recent Advances in Natural Product-Based Hybrids as Anti-Cancer Agents
Sflakidou, E., Leonidis, G., Foroglou, E., Siokatas, C., & Sarli, V. (2022) · Molecules · doi:10.3390/molecules27196632 · Cited by 49 · see citing works
Zhao, Z., Nian, M., Qiao, H., Yang, X., Wu, S., & Zheng, X. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114733 · Cited by 47 · see citing works
Xu, F., Zhang, X., Chen, Z., He, S., Guo, J., Yu, L., Wang, Y., Hou, C., AI-furas, H., Zheng, Z., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01246 · Cited by 47 · see citing works
Self-citationApplication and challenges of nitrogen heterocycles in PROTAC linker
Li, Y., Qu, J., Jiang, L., Peng, X., Wu, K., Chen, M., Peng, Y., & Cao, X. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116520 · Cited by 45 · see citing works
Self-citationProteases and Their Modulators in Cancer Therapy: Challenges and Opportunities
Song, R., Qiao, W., He, J., Huang, J., Luo, Y., & Yang, T. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01640 · Cited by 45 · see citing works
Development of PROTAC degrader probe of CDK4/6 based on DCAF16
Pu, C., Liu, Y., Deng, R., Xu, Q., Wang, S., Zhang, H., Luo, D., Ma, X., Tong, Y., Ma, X., et al. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106637 · Cited by 43 · see citing works
The application of PROTAC in HDAC
Chen, S., Zheng, Y., Liang, B., Yin, Y., Yao, J., Wang, Q., Liu, Y., & Neamati, N. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115746 · Cited by 43 · see citing works
P-TEFb as A Promising Therapeutic Target
Fujinaga, K. (2020) · Molecules · doi:10.3390/molecules25040838 · Cited by 43 · see citing works
PROTACS: A technology with a gold rush-like atmosphere
Wang, Y., Lan, L., Wang, M., Zhang, J., Gao, Y., Shi, L., & Sun, L. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.115037 · Cited by 42 · see citing works
Self-citationChen, S., Bi, K., Liang, H., Wu, Z., Huang, M., Chen, X. X., Dong, G., & Sheng, C. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.10.014 · Cited by 43 · see citing works
Rana, S., Mallareddy, J. R., Singh, S., Boghean, L., & Natarajan, A. (2021) · Cancers · doi:10.3390/cancers13215506 · Cited by 42 · see citing works
Cereblon-Recruiting PROTACs: Will New Drugs Have to Face Old Challenges?
Cieślak, M., & Słowianek, M. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15030812 · Cited by 41 · see citing works
Cassandri, M., Fioravanti, R., Pomella, S., Valente, S., Rotili, D., Baldo, G. D., Angelis, B. D., Rota, R., & Mai, A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01230 · Cited by 39 · see citing works
Maneiro, M., Vita, E. D., Conole, D., Kounde, C. S., Zhang, Q., & Tate, E. W. (2021) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2021.01.002 · Cited by 38 · see citing works
Light-Controllable PROTACs for Temporospatial Control of Protein Degradation
Liu, J., Peng, Y., & Wei, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.678077 · Cited by 38 · see citing works
Natural Product-Inspired Targeted Protein Degraders: Advances and Perspectives
Li, J., Cai, Z., Li, X., & Zhuang, C. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01223 · Cited by 37 · see citing works
Wu, T., Zhang, Z., Gong, G., Xu, Y., Xu, Y., Yu, S., Ma, F., Zhang, X., Wang, Y., Chen, H., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115774 · Cited by 35 · see citing works
Self-citationTranscriptional cyclin-dependent kinases: Potential drug targets in cancer therapy
Liu, Y., Fu, L., Wu, J., Liu, M., Wang, G., Liu, B., & Zhang, L. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.114056 · Cited by 35 · see citing works
CDK9 inhibitors in cancer research
Huang, Z. L., Wang, T., Wang, C., & Fan, Y. L. (2022) · RSC Medicinal Chemistry · doi:10.1039/d2md00040g · Cited by 34 · see citing works
Small-molecule PROTACs: Novel Agents for Cancer Therapy
Wan, Y., Yan, C., Gao, H. J., & Liu, T. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0340 · Cited by 32 · see citing works
Construction of an IMiD-based azide library as a kit for PROTAC research
Liu, H., Sun, R., Ren, C., Qiu, X., Yang, X., & Jiang, B. (2020) · Organic & Biomolecular Chemistry · doi:10.1039/d0ob02120b · Cited by 30 · see citing works
Progress of small molecules for targeted protein degradation: PROTACs and other technologies
Zhao, H., Xin, M., & Zhang, S. (2023) · Drug Development Research · doi:10.1002/ddr.22026 · Cited by 31 · see citing works
Abbas, A., & Ye, F. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.134293 · Cited by 29 · see citing works
Natural product-based PROteolysis TArgeting Chimeras (PROTACs)
Liu, M., Martyn, A. P., & Quinn, R. J. (2022) · Natural Product Reports · doi:10.1039/d2np00038e · Cited by 28 · see citing works
Tokarski, R. J., Sharpe, C., Huntsman, A. C., Mize, B. K., Ayinde, O. R., Stahl, E. H., Lerma, J. R., Reed, A., Carmichael, B., Muthusamy, N., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115342 · Cited by 28 · see citing works
PROTAC unleashed: Unveiling the synthetic approaches and potential therapeutic applications
Pravin, N., & Jóźwiak, K. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116837 · Cited by 28 · see citing works
Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues
Marei, H. E. S., Bedair, K., Hasan, A., Al-Mansoori, L., Gaiba, A., Morrione, A., Cenciarelli, C., & Giordano, A. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-00931-8 · Cited by 30 · see citing works
Addressing Transcriptional Dysregulation in Cancer through CDK9 Inhibition
Toure, M. A., & Koehler, A. N. (2023) · Biochemistry · doi:10.1021/acs.biochem.2c00609 · Cited by 25 · see citing works
Advances of bioorthogonal coupling reactions in drug development
Zhan, F., Zhu, J., Xie, S., Xu, J., & Xu, S. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115338 · Cited by 24 · see citing works
Emerging approaches to CDK inhibitor development, a structural perspective
Hope, I., Endicott, J., & Watt, J. E. (2022) · RSC Chemical Biology · doi:10.1039/d2cb00201a · Cited by 22 · see citing works
Rational Proteolysis Targeting Chimera Design Driven by Molecular Modeling and Machine Learning
Tan, S., Chen, Z., Lu, R., Liu, H., & Yao, X. (2025) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.70013 · Cited by 23 · see citing works
Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs
Vicente, A. T. S., Moura, S. P. S. P., & Salvador, J. A. R. (2025) · Communications Chemistry · doi:10.1038/s42004-025-01598-9 · Cited by 23 · see citing works
Wu, M., Han, J., Liu, Z., Zhang, Y., Huang, C. Z., Li, J., & Zeng, L. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118228 · Cited by 22 · see citing works
Targeted degradation of CDK9 potently disrupts the MYC-regulated network
Toure, M. A., Motoyama, K., Xiang, Y., Urgiles, J., Kabinger, F., Koglin, A.-S., Iyer, R. S., Gagnon, K., Kumar, A., Ojeda, S., et al. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.03.001 · Cited by 22 · see citing works
Computational strategies for PROTAC drug discovery
Wu, J., Wang, W., & Leung, C. (2023) · Acta Materia Medica · doi:10.15212/amm-2022-0041 · Cited by 20 · see citing works
Zhong, Y., Xu, J., Cao, H., Gao, J., Ding, S., Ren, Z., Yang, H., Sun, Y., Cheng, M., Li, J., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.03.047 · Cited by 18 · see citing works
Biology of Pellino1: a potential therapeutic target for inflammation in diseases and cancers
Yan, L., Cui, Y., & Feng, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1292022 · Cited by 18 · see citing works
Asghar, A., Chohan, T. A., Khurshid, U., Saleem, H., Mustafa, M. W., Khursheed, A., Alafnan, A. D., Batul, R., Break, M. K. B., Almansour, K., et al. (2024) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2024.110940 · Cited by 18 · see citing works
Ubiquitin–proteasome system-targeted therapy for uveal melanoma: what is the evidence?
Zhao, C., Zeng, C., Wang, K., He, Q., Yang, B., Zhou, F., & Zhu, H. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0441-3 · Cited by 18 · see citing works
Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications
Li, Q., Zhou, L., Qin, S., Huang, Z., Li, B., Li, B., Yang, M., Nice, E. C., Zhu, H., & Huang, C. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115447 · Cited by 17 · see citing works
Liu, R., Qian, M., & Cui, Y. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155665 · Cited by 16 · see citing works
CDK9 targeting PROTAC L055 inhibits ERα-positive breast cancer
Chen, W., Wu, Y., Yang, C., Ren, W., Hou, L., Liang, H., Wu, T., Kong, Y., Wu, J., Rao, Y., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116972 · Cited by 16 · see citing works
Proteolysis-targeting Chimeras for Targeting Protein for Degradation
Qi, J., & Zhang, G. (2019) · Future Medicinal Chemistry · doi:10.4155/fmc-2018-0557 · Cited by 15 · see citing works
Protein-Targeted Degradation Agents Based on Natural Products
Li, Y., Jia, Y., Wang, X., Shang, H., & Tian, Y. P. (2022) · Pharmaceuticals · doi:10.3390/ph16010046 · Cited by 14 · see citing works
Self-citationDiscovery of HyT‐Based Degraders of CDK9‐Cyclin T1 Complex
Lin, R., Yang, J., Liu, T., Wang, M., Ke, C., Luo, C., Lin, J. H., Li, J., & Lin, H. (2023) · Chemistry & Biodiversity · doi:10.1002/cbdv.202300769 · Cited by 15 · see citing works
Yang, H., Qin, J., Pei, Y., Guan, S., Zhao, M., Wang, Y., Yao, Y., Duan, Y., & Sun, M. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.116067 · Cited by 14 · see citing works
Self-citationPROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras
Bhole, R. P., Patil, S., Kapare, H. S., Chikhale, R. V., & Gurav, S. S. (2024) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266309968240621072550 · Cited by 14 · see citing works
Cereblon: promise and challenges for combating human diseases
Kim, H. K., Seol, J. E., Ahn, S. W., Jeon, S., Park, C., & Han, J. (2021) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-021-02624-0 · Cited by 14 · see citing works
Chimera induced protein degradation: PROTACs and beyond
Yin, L., & Hu, Q. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112494 · Cited by 14 · see citing works
Development of natural product-based targeted protein degraders as anticancer agents
Chen, C., Feng, Y., Zhou, C., Liu, Z., Tang, Z., Zhang, Y., Li, T., Gu, C., & Chen, J. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107772 · Cited by 13 · see citing works
Self-citationWang, Y., Wang, M., Lan, M., Zhang, Y., Jiao, Y., Zhang, S., Yang, Y., Li, J., Wei, M., Cao, S., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01621 · Cited by 13 · see citing works
Self-citationSmall-Molecule Degraders of Cyclin-Dependent Kinase Protein: A Review
Yu, B., Du, Z., Zhang, Y., Li, Z., & Bian, J. (2021) · Future Medicinal Chemistry · doi:10.4155/fmc-2021-0154 · Cited by 13 · see citing works
Self-citationRecent Advances in the Design and Development of Anticancer Molecules based on PROTAC Technology
Mukhamejanova, Z., Tong, Y., Xiang, Q., Xu, F., & Pang, J. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200312112412 · Cited by 13 · see citing works
DNA-modularized construction of bivalent ligands precisely regulates receptor binding and activation
Zhao, N., Wu, W., Wang, Y., Song, K., Chen, G., Chen, Y., Wang, R., Xu, J., Cui, K., Chen, H., et al. (2023) · Chem · doi:10.1016/j.chempr.2022.12.002 · Cited by 12 · see citing works
Self-citationNie, H., Li, B., Sun, J., Yuan, Y., Zhang, Z., Hu, H., Wang, W., Chen, Z., Wang, S., Huang, W., et al. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107876 · Cited by 12 · see citing works
- Authors
- Bian, J., Ren, J., Li, Y., Wang, J., Xu, X., Feng, Y., Tang, H., Wang, Y., & Li, Z.
- Affiliations
- China Pharmaceutical University (CN)
- Corresponding author
- Bian, Jinlei
- Li, Yongren
- Wang, Jubo
- Wang, Yajing
- Li, Zhiyu
- Venue
- Bioorganic Chemistry
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 81
- Pages
- 373-381
- ISSN
- 0045-2068 (ISSN-L)
- OpenAlex
- W2888785247
- Cited by
- 140
- References
- 17
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 18 · 2023: 22 · 2022: 20 · 2021: 20 · 2020: 21 · 2019: 13
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation (81703347)
- Natural Science Foundation of Jiangsu Province (BK20170743)
- Fundamental Research Funds for the Central Universities, China (2632017PY13)
- R&D of Novel Drugs (J1310032)
- National Found for Fostering Talents of Basic Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- wogonin, PROTACs, CDK9, cereblon, click chemistry, triazole linkers, protein degradation, proteasomal degradation, anticancer activity, Scutellaria baicalensis, natural product scaffolds
- MeSH terms
- Antineoplastic Agents, Humans, Neoplasms, Peptide Hydrolases, Cyclin-Dependent Kinase 9, Ubiquitin-Protein Ligases, Flavanones, Protein Kinase Inhibitors, Adaptor Proteins, Signal Transducing, Drug Discovery, Click Chemistry, Proteolysis, MCF-7 Cells, Molecular Docking Simulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
