Discovery of highly potent, selective, covalent inhibitors of JAK3

The JAK-STAT Pathway at Twenty

Stark, G. R., & Darnell, J. E., Jr. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.013 · Cited by 1,523 · see citing works

JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease

O’Shea, J. J., & Plenge, R. M. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.014 · Cited by 1,146 · see citing works

Developing Irreversible Inhibitors of the Protein Kinase Cysteinome

Liu, Q., Sabnis, Y. A., Zhao, Z., Zhang, T., Buhrlage, S. J., Jones, L. H., & Gray, N. S. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.12.006 · Cited by 662 · see citing works

Discovery and Development of Janus Kinase (JAK) Inhibitors for Inflammatory Diseases

Clark, J. D., Flanagan, M. E., & Telliez, J. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401490p · Cited by 615 · see citing works

Chemical and Computational Methods for the Characterization of Covalent Reactive Groups for the Prospective Design of Irreversible Inhibitors

Flanagan, M. E., Abramite, J. A., Anderson, D. P., AULABAUGH, A. E., Dahal, U. P., Gilbert, A. M., Li, C., Montgomery, J. I., Oppenheimer, S. R., Ryder, T. F., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501412a · Cited by 337 · see citing works

Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection.

Flanagan, M., Blumenkopf, T., Brissette, W., Brown, M. F., Casavant, J. M., Chang, S.-P., Doty, J. L., Elliott, E., Fisher, M., Hines, M., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm1004286 · Cited by 334 · see citing works

Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition

Telliez, J.-B., Dowty, M. E., Wang, L., Jussif, J., Lin, T., Li, L., Moy, E., Balbo, P., Li, W., Zhao, Y., et al. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00677 · Cited by 204 · see citing works

Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2<i>S</i>,5<i>R</i>)-5-((7<i>H</i>-Pyrrolo[2,3-<i>d</i>]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans

Thorarensen, A., Dowty, M. E., Banker, M. E., Juba, B., Jussif, J., Lin, T., Vincent, F., Czerwinski, R. M., Casimiro-Garcia, A., Unwalla, R., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01694 · Cited by 176 · see citing works

Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls

Kumalo, H., Bhakat, S., & Soliman, M. (2015) · Molecules · doi:10.3390/molecules20021984 · Cited by 158 · see citing works

Development of Selective Covalent Janus Kinase 3 Inhibitors

Tan, L., Akahane, K., McNally, R., Reyskens, K. M. S. E., Ficarro, S. B., Liu, S., Herter-Sprie, G. S., Koyama, S., Pattison, M. J., Labella, K., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00710 · Cited by 122 · see citing works

Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol

Goedken, E. R., Argiriadi, M. A., Banach, D. L., Fiamengo, B. A., Foley, S. E., Frank, K. E., George, J. S., Harris, C. M., Hobson, A. D., Ihle, D. C., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.595181 · Cited by 101 · see citing works

Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling

Smith, G. A., Uchida, K., Weiss, A., & Taunton, J. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2056 · Cited by 86 · see citing works

Discovery and structure–activity relationship studies of irreversible benzisothiazolinone-based inhibitors against Staphylococcus aureus sortase A transpeptidase

Zhulenkovs, D., Rudevica, Z., Jaudzems, K., Turks, M., & Leonchiks, A. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.09.011 · Cited by 71 · see citing works

Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)

Lucca, G. V. D., Shi, Q., Liu, Q., Batt, D. G., Bertrand, M. B., Rampulla, R., Mathur, A., Discenza, L., D’Arienzo, C. J., Dai, J., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00722 · Cited by 57 · see citing works

Discovery of pyrrolo[1,2-b]pyridazine-3-carboxamides as Janus kinase (JAK) inhibitors

Duan, J. J. ‐., Lu, Z., Jiang, B., Yang, B. V., Doweyko, L. M., Nirschl, D. S., Haque, L., Lin, S., Brown, G. D., Hynes, J. J., et al. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.10.061 · Cited by 30 · see citing works

Discovery of potent and efficacious pyrrolopyridazines as dual JAK1/3 inhibitors

Hynes, J. J., Wu, H., Kempson, J., Duan, J. J. ‐., Lu, Z., Jiang, B., Stachura, S., Tokarski, J. S., Sack, J. S., Khan, J., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.05.043 · Cited by 14 · see citing works

Review of tofacitinib in rheumatoid arthritis

Lopez-Olivo, M. A., Lu, H., & Tayar, J. H. (2015) · Clinical Investigation · doi:10.4155/cli.14.107 · Cited by 12 · see citing works

Advances in covalent drug discovery

Boike, L., Henning, N. J., & Nomura, D. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00542-z · Cited by 823 · see citing works

Covalent inhibitors: a rational approach to drug discovery

Sutanto, F., Konstantinidou, M., & Dömling, A. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00154f · Cited by 389 · see citing works

An electrophilic warhead library for mapping the reactivity and accessibility of tractable cysteines in protein kinases

Petri, L., Egyed, A., Bajusz, D., Imre, T., Hetényi, A., Martinek, T. A., Ábrányi‐Balogh, P., & Keserű, G. M. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112836 · Cited by 49 · see citing works

Pharmacological Modulation of the Crosstalk between Aberrant Janus Kinase Signaling and Epigenetic Modifiers of the Histone Deacetylase Family to Treat Cancer

Mustafa, A. M., & Krämer, O. H. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000612 · Cited by 42 · see citing works

Discovery of an Orally Available Janus Kinase 3 Selective Covalent Inhibitor

Shi, L., Zhong, Z., Li, X., Zhou, Y., & Pan, Z. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01823 · Cited by 37 · see citing works

Covalent inhibitors: An ambitious approach for the discovery of newer oncotherapeutics

Cheke, R. S., & Kharkar, P. S. (2023) · Drug Development Research · doi:10.1002/ddr.22132 · Cited by 22 · see citing works

A perspective on the changing landscape of HTS

Lanne, A., Usselmann, L. E. J., Llowarch, P., Michaelides, I. N., Fillmore, M. C., & Holdgate, G. A. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103670 · Cited by 20 · see citing works

Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors

Yu, R.-N., Chen, C., Shu, L., Yin, Y., Wang, Z., Zhang, T., & Zhang, D. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.03.009 · Cited by 20 · see citing works

Essential Kinases and Transcriptional Regulators and Their Roles in Autoimmunity

Deng, Y., Bellanti, J. A., & Zheng, S. G. (2019) · Biomolecules · doi:10.3390/biom9040145 · Cited by 20 · see citing works

Current Status in the Discovery of Covalent Janus Kinase 3 (JAK3) Inhibitors

Dai, J., Yang, L., & Addison, G. (2019) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557519666190617152011 · Cited by 19 · see citing works

JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma

Chi, F., Chen, L., Wang, C., Li, L., Sun, X., Xu, Y., Ma, T., Liu, K., Ma, X., & Shu, X. H. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.103542 · Cited by 17 · see citing works

The Current Toolbox for Covalent Inhibitors: From Hit Identification to Drug Discovery

You, M., Liu, H., & Li, C. (2025) · JACS Au · doi:10.1021/jacsau.5c01134 · Cited by 17 · see citing works

Design, synthesis, and biological evaluation of cyano-substituted 2,4-diarylaminopyrimidines as potent JAK3 inhibitors for the treatment of B-cell lymphoma

Wu, B., Yang, S., Deng, T., Wang, C., Jin, Y., Yu, J., Xu, Y., Chen, L., Li, Y., & Ma, X. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105330 · Cited by 15 · see citing works

Discovery of a JAK1/3 Inhibitor and Use of a Prodrug To Demonstrate Efficacy in a Model of Rheumatoid Arthritis

Spergel, S. H., Mertzman, M., Kempson, J., Guo, J., Stachura, S., Haque, L., Lippy, J., Zhang, R. F., Galella, M. A., Pitt, S., et al. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.8b00508 · Cited by 14 · see citing works

In Ovo Injection of CHIR-99021 Promotes Feather Follicle Development via Modulating the Wnt Signaling Pathway and Transcriptome in Goose Embryos (Anser cygnoides)

Feng, Z., Gong, H., Fu, J., Xu, X., Song, Y., Yan, X., Mabrouk, I., Zhou, Y., Wang, Y., Fu, X., et al. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.858274 · Cited by 13 · see citing works

Best Practices for Design and Characterization of Covalent Chemical Probes

Gabizon, R., Resnick, E., & London, N. (2020) · Royal Society of Chemistry eBooks · doi:10.1039/9781839160745-00069 · Cited by 10 · see citing works

Identification of novel covalent JAK3 inhibitors through consensus scoring virtual screening: integration of common feature pharmacophore and covalent docking

Qiu, G., Yu, L., Jia, L., Cai, Y., Chen, Y., Jin, J., Xu, L., & Zhu, J. (2024) · Molecular Diversity · doi:10.1007/s11030-024-10918-5 · Cited by 9 · see citing works

Covalent Modification of the JH2 Domain of Janus Kinase 2

Henry, S. P., Liosi, M.-E., Ippolito, J. A., Menges, F., Newton, A. S., Schlessinger, J., & Jorgensen, W. L. (2022) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.2c00414 · Cited by 8 · see citing works

Design of Rational JAK3 Inhibitors Based on the Parent Core Structure of 1,7-Dihydro-Dipyrrolo [2,3-b:3′,2′-e] Pyridine

Li, Y., Meng, D., Xie, J., Li, R., Wang, Z., Li, J., Mou, L., Deng, X., & Deng, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105437 · Cited by 8 · see citing works

Covalent Targeting Leads to the Development of a LIMK1 Isoform-Selective Inhibitor

Mandel, S., Hanke, T., Prendiville, N., Baena-Nuevo, M., Berger, L. M., Farges, F., Schwalm, M. P., Berger, B., Krämer, A., Elson, L., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01204 · Cited by 6 · see citing works

Methods for the synthesis of pyrrolo[1,2-b]pyridazine and pyrrolo[1,2-b]cinnoline derivatives (microreview)

Plieva, A. T. (2019) · Chemistry of Heterocyclic Compounds · doi:10.1007/s10593-019-02441-5 · Cited by 6 · see citing works

Are peptides a solution for the treatment of hyperactivated JAK3 pathways?

Dullius, A., Rocha, C. M., Laufer, S., de Souza, C. F. V., & Goettert, M. I. (2019) · Inflammopharmacology · doi:10.1007/s10787-019-00589-2 · Cited by 6 · see citing works

Novel synthetic approach to pyrrolo[1,2-b]cinnolines

Plieva, A. T., Chalikidi, P. N., Gutnov, A. V., Turiev, A. M., Демидов, О. П., Aksenov, N. A., Magkoev, T. T., & Abaev, V. T. (2020) · Chemistry of Heterocyclic Compounds · doi:10.1007/s10593-020-02770-w · Cited by 5 · see citing works

Covalent Janus Kinase 3 Inhibitors

Gehringer, M., & Förster, M. (2020) · Topics in medicinal chemistry · doi:10.1007/7355_2020_96 · Cited by 4 · see citing works

Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts

Wang, L. L., Tuohy, S., Xu, K. L., Nace, A., Yang, R., Zheng, Y., Burdick, J. A., & Cotsarelis, G. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303256 · Cited by 3 · see citing works

Dual Targeting of Janus Kinase and Bruton’s Tyrosine Kinase: A New Approach to Control the Pathogenesis of Rheumatoid Arthritis

Pery, N., Ijaz, F., Rizvi, N. B., Munawar, M. A., & Shafiq, M. I. (2020) · Pakistan Journal of Zoology · doi:10.17582/journal.pjz/20191010081058 · Cited by 2 · see citing works

Pharmacophore Modeling of Janus Kinase Inhibitors: Tools for Drug Discovery and Exposition Prediction

Fischer, F., Temml, V., & Schuster, D. (2025) · Molecules · doi:10.3390/molecules30102183 · Cited by 1 · see citing works

JAK Family Inhibitors for Autoimmune Diseases

Borzilleri, R. M., Hart, A. C., Moslin, R. M., Tokarski, J. S., & Wrobleski, S. T. (2021) · Burger's Medicinal Chemistry and Drug Discovery · doi:10.1002/0471266949.bmc279

Research Progress on Virtual Screening Design Techniques for Small Molecule Inhibitors of JAK3 Kinase

迟, 宪. (2025) · Hans Journal of Medicinal Chemistry · doi:10.12677/hjmce.2025.131011

Effective virtual screening strategy toward JAK3 covalent inhibitors: combining multi‑conformational consensus calculation with covalent docking

Zhu, J., Qiu, G., Xu, L., Cai, Y., Chen, Y., & Jin, J. (2025) · Molecular Diversity · doi:10.1007/s11030-025-11329-w

Development of small molecules modulating the activity of the nucleoside kinase dCK

Yaala, K. B. (2021) · doi:10.70675/749d80bcze0abz4780za87czd786c1617d69

Why JAK3 selectivity matters: biology, approved JAK inhibitors, and medicinal chemistry perspectives

da Silva, S. D., & Parise-Filho, R. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110298

BindingDB Entry 50007306: Discovery of an Orally Available Janus Kinase 3 Selective Covalent Inhibitor.

BindingDB (2021) · UC San Diego · doi:10.7270/q20g3pfp

BindingDB Entry 50007482: Discovery of a JAK1/3 Inhibitor and Use of a Prodrug To Demonstrate Efficacy in a Model of Rheumatoid Arthritis.

BindingDB (2021) · UC San Diego · doi:10.7270/q2z03cg8

BindingDB Entry 50010326: Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors.

BindingDB (2021) · UC San Diego · doi:10.7270/q2pc35wg

BindingDB Entry 50016591: Covalent Modification of the JH2 Domain of Janus Kinase 2.

BindingDB (2023) · UC San Diego · doi:10.7270/q2d50rzq

BindingDB Entry 50018380: An electrophilic warhead library for mapping the reactivity and accessibility of tractable cysteines in protein kinases.

BindingDB (2024) · UC San Diego · doi:10.7270/q2zw1r4j

Design, synthesis, and SAR study of highly potent, selective, irreversible covalent JAK3 inhibitors

He, L., Shao, M., Wang, T., Lan, T., Zhang, C., & Chen, L. (2018) · Molecular Diversity · doi:10.1007/s11030-017-9803-2 · Cited by 24 · see citing works

Development of Selective Covalent Janus Kinase 3 Inhibitors

Tan, L., Akahane, K., McNally, R., Reyskens, K. M. S. E., Ficarro, S. B., Liu, S., Herter-Sprie, G. S., Koyama, S., Pattison, M. J., Labella, K., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00710 · Cited by 122 · see citing works

Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket

Förster, M., Chaikuad, A., Bauer, S. M., Holstein, J., Robers, M. B., Corona, C. R., Gehringer, M., Pfaffenrot, E., Ghoreschi, K., Knapp, S., et al. (2016) · Cell chemical biology · doi:10.1016/j.chembiol.2016.10.008 · Cited by 132 · see citing works

Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors

Casimiro‐Garcia, A., Trujillo, J. I., Vajdos, F. F., Juba, B. M., Banker, M. E., AULABAUGH, A. E., Balbo, P., Bauman, J. N., Chrencik, J., Coe, J. W., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01308 · Cited by 84 · see citing works

Development, Optimization, and Structure–Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4-d]pyrrolo[2,3-b]pyridine Scaffold

Förster, M., Chaikuad, A., Dimitrov, T., Döring, E., Holstein, J., Berger, B., Gehringer, M., Ghoreschi, K., Müller, S., Knapp, S., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00571 · Cited by 63 · see citing works