Illuminating Function of the Understudied Druggable Kinome

Gary L. Johnson, Ph.D.
Kenan Distinguished Professor and Chair
Department of Pharmacology
School of Medicine
School of Medicine
University of North Carolina, Chapel Hill

Contacts/Links

Harvard Program in Therapeutic Science:
@shawnmgomez

Overview

Dr. Gary L. Johnson has established a network of collaborators; Dr. Shawn Gomez (UNC), Dr. Ben Major (UNC), Dr. Tim Willson (SGC), Dr. Reid Townsend (WU), and Dr. Peter Sorger (HMS), to tackle the illumination of function of the understudied druggable kinome. Their work includes technologies of Multiplex Inhibitor Beads (MIB) / Mass Spectrometry (MS) to identify kinase activation status in response to perturbants, and applied to model cell lines and Patient Derived xenographs. These information along with collection of other data will be incorporated in the building of a Dark Kinase Knowledgebase (DKK) that provides gene-by-gene and network-level information on the dark kinome and its interaction with other signal transduction and regulatory networks.

NIH grant number:  1U24DK116204-01

Progress on IDG project as tracked by Protein Illumination Timeline:
Kinase Chemical Tools: https://druggablegenome.net/ProteinTimelineKinaseChemicalTools
Kinase Proteomics: https://druggablegenome.net/ProteinTimelineKinaseProteomics

Informatic resources developed by DRGC-Kinase:
Dark Kinome Knowledgebase: https://darkkinome.org/

GITHUB LINK: 134 Kinase https://github.com/sorgerlab/DarkKinome

Additional collaborators:

  • Shawn Gomez, Ph.D.

Associate Professor in Department of Biomedical Engineering
Adjunct Assistant Professor in Department of Computer Science

  • Ben Major, Ph.D.

Associate Professor in Department of Cell Biology & Physiology
Assistant Professor in Department of Computer Science

  • Tim Willson, Ph.D.

Chief Scientist at Structural Genomics Consortium
Research Professor at Eshelman School of Pharmacy
University of North Carolina, Chapel Hill

  • Reid Townsend, M.D., Ph.D.

Professor of Medicine
Director, Mass Spectrometry Resource
Washington University in St. Louis

  • Peter Sorger, Ph.D

Otto Krayer Professor
Systems Pharmacology
Harvard Medical School

DRGC-Kinase Publications:

  1. Pozzetti L, East MP, Laitinen T, Asquith CRM. TLK2: a target for cancer and viral latency. Nature Rev Drug Disc. 2024 Oct 17. doi: https://doi.org/10.1038/d41573-024-00163-8
  2. East MP, Sprung RW, Okumu DO, Olivares-Quintero JF, Joisa CU, Chen X, Zhang Q, Erdmann-Gilmore P, Mi Y, Sciaky N, Malone JP, Bhatia S, McCabe IC, Xu Y, Sutcliffe MD, Luo J, Spears PA, Perou CM, Earp HS, Carey LA, Yeh JJ, Spector DL, Gomez SM, Spanheimer PM, Townsend RR, Johnson GL. Quantitative proteomic mass spectrometry of protein kinases to determine dynamic heterogeneity of the human kinome. bioRxiv [Preprint]. 2024 Oct 4:2024.10.04.614143. doi: 10.1101/2024.10.04.614143. PMID: 39464086
  3. Berginski ME, Jenner MR, Joisa CU, Herrera Loeza G, Golitz BT, Lipner MB, Leary JR, Rashid N, Johnson GL, Yeh JJ, Gomez SM. Kinome state is predictive of cell viability in pancreatic cancer tumor and cancer-associated fibroblast cell lines. PeerJ. 2024 Aug 28;12:e17797. doi: 10.7717/peerj.17797. eCollection 2024. PMID: 39221276
  4. Kirchoff KE, Wellnitz J, Hochuli JE, Maxfield T, Popov KI, Gomez S, Tropsha A. Utilizing Low-Dimensional Molecular Embeddings for Rapid Chemical Similarity Search. Adv Inf Retr. 2024 Mar:14609:34-49. doi: 10.1007/978-3-031-56060-6_3. Epub 2024 Mar 16. PMID: 38585224 Publication Date:Mar 16, 2024 https://doi.org/10.1007/978-3-031-56060-6_3
  5. Bashore FM, Min SM, Chen X, Howell S, Rinderle CH, Morel G, Silvaroli JA, Wells CI, Bunnell BA, Drewry DH, Pabla NS, Ultanir SK, Bullock AN, Axtman AD.Discovery and Characterization of a Chemical Probe for Cyclin-Dependent Kinase-Like 2. bioRxiv [Preprint]. 2024 May 14:2024.05.12.593776. doi: 10.1101/2024.05.12.593776. PMID: 38798634 Publication Date:July 3, 2024 https://doi.org/10.1021/acsmedchemlett.4c00219
  6. Karim M, Mishra M, Lo CW, Saul S, Cagirici HB, Tran DHN, Agrawal A, Ghita L, Ojha A, East MP, Gammeltoft KA, Sahoo MK, Johnson GL, Das S, Jochmans D, Cohen CA, Gottwein J, Dye J, Neff N, Pinsky BA, Laitinen T, Pantsar T, Poso A, Zanini F, Jonghe S, Asquith CRM, Einav S. PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2. bioRxiv [Preprint]. 2024 Apr 17:2024.04.15.589676. doi: 10.1101/2024.04.15.589676. PMID: 38659941.
  7. Asquith CRM, East MP, Laitinen T, Alamillo-Ferrer C, Hartikainen E, Wells CI, Axtman AD, Drewry DH, Tizzard GJ, Poso A, Willson TM, Johnson GL. Discovery and optimization of narrow spectrum inhibitors of Tousled like kinase 2 (TLK2) using quantitative structure activity relationships. European Journal of Medicinal Chemistry. Volume 271, 5 May 2024, 116357 doi:10.1016/j.ejmech.2024.116357.  PMID: 38636130.
  8. Gomez SM, Axtman AD, Willson TM, Major MB, Townsend RR, Sorger PK, Johnson GL. Illuminating function of the understudied druggable kinome. Drug Discov Today. 2024 Mar;29(3):103881. doi: 10.1016/j.drudis.2024.103881. Epub 2024 Jan 11. PMID: 38218213.
  9. Asressu KH, Smith JL, Dickmander RJ, Moorman NJ, Wellnitz J, Popov KI, Axtman AD, Willson TM. Synthesis of 5-Benzylamino and 5-Alkylamino-Substituted Pyrimido[4,5-c]quinoline Derivatives as CSNK2A Inhibitors with Antiviral Activity. Pharmaceuticals (Basel). 2024 Feb 27;17(3):306. doi: 10.3390/ph17030306. PMID: 38543092
  10. Galal KA, Krämer A, Strickland BG, Smith JL, Dickmander RJ, Moorman NJ, Willson TM. Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3. bioRxiv [Preprint]. 2023 Dec 5:2023.12.04.569845. doi: 10.1101/2023.12.04.569845. Update in: Bioorg Med Chem Lett. 2024 Jan 8;99:129617. PMID: 38106118; PMCID: PMC10723276.
  11. Joisa CU, Chen KA, Berginski ME, Golitz BT, Jenner MR, Herrera Loeza G, Yeh JJ, Gomez SM. Integrated single-dose kinome profiling data is predictive of cancer cell line sensitivity to kinase inhibitors. PeerJ. 2023 Nov 16;11:e16342. doi: 10.7717/peerj.16342. PMID: 38025707; PMCID: PMC10657565.
  12. Tiek D, Wells CI, Schröder M, Song X, Alamillo-Ferrer C, Goenka A, Iglesia R, Lu M, Hu B, Kwarcinski F, Sintha P, de Silva C, Hossain MA, Picado A, Zuercher W, Zutshi R, Knapp S, Riggins RB, Cheng SY, Drewry DH. SGC-CLK-1: A chemical probe for the Cdc2-like kinases CLK1, CLK2, and CLK4. Curr Res Chem Biol. 2023;3:100045. doi: 10.1016/j.crchbi.2023.100045. Epub 2023 Sep 22. PMID: 38009092; PMCID: PMC10673624.
  13. Chen H, Lye MF, Gorgulla C, Ficarro SB, Cuny GD, Scott DA, Wu F, Rothlauf PW, Wang X, Fernandez R, Pesola JM, Draga S, Marto JA, Hogle JM, Arthanari H, Coen DM. A small molecule exerts selective antiviral activity by targeting the human cytomegalovirus nuclear egress complex. PLoS Pathog. 2023 Nov 17;19(11):e1011781. doi: 10.1371/journal.ppat.1011781. PMID: 37976321; PMCID: PMC10691697.
  14. Cruite JT, Nowak RP, Donovan KA, Ficarro SB, Huang H, Liu H, Liu Y, Marto JA, Metivier RJ, Fischer ES, Jones LH. Covalent Stapling of the Cereblon Sensor Loop Histidine Using Sulfur-Heterocycle Exchange. ACS Med Chem Lett. 2023 Oct 24;14(11):1576-1581. doi: 10.1021/acsmedchemlett.3c00371. PMID: 37974938; PMCID: PMC10641907.
  15. Nowak RP, Ragosta L, Huerta F, Liu H, Ficarro SB, Cruite JT, Metivier RJ, Donovan KA, Marto JA, Fischer ES, Zerfas BL, Jones LH. Development of a covalent cereblon-based PROTAC employing a fluorosulfate warhead. RSC Chem Biol. 2023 Aug 31;4(11):906-912. doi: 10.1039/d3cb00103b. PMID: 37920397; PMCID: PMC10619143.
  16. Yang X, Ong HW, Dickmander RJ, Smith JL, Brown JW, Tao W, Chang E, Moorman NJ, Axtman AD, Willson TM. Optimization of 3-Cyano-7-cyclopropylamino- pyrazolo[1,5-a]pyrimidines toward the Development of an In Vivo Chemical Probe for CSNK2A. ACS Omega. 2023 Oct 10;8(42):39546-39561. doi: 10.1021/acsomega.3c05377. PMID: 37901516; PMCID: PMC10600890.
  17. Wamsley NT, Wilkerson EM, Guan L, LaPak KM, Schrank TP, Holmes BJ, Sprung RW, Gilmore PE, Gerndt SP, Jackson RS, Paniello RC, Pipkorn P, Puram SV, Rich JT, Townsend RR, Zevallos JP, Zolkind P, Le QT, Goldfarb D, Major MB. Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC. Mol Cell Proteomics. 2023 Nov;22(11):100647. doi: 10.1016/j.mcpro.2023.100647. Epub 2023 Sep 15. PMID: 37716475; PMCID: PMC10587640.
  18. Anderson B, Rosston P, Ong HW, Hossain MA, Davis-Gilbert ZW, Drewry DH. How many kinases are druggable? A review of our current understanding. Biochem J. 2023 Aug 30;480(16):1331-1363. doi: 10.1042/BCJ20220217. PMID: 37642371; PMCID: PMC10586788.
  19. Fritch EJ, Mordant AL, Gilbert TSK, Wells CI, Yang X, Barker NK, Madden EA, Dinnon KH 3rd, Hou YJ, Tse LV, Castillo IN, Sims AC, Moorman NJ, Lakshmanane P, Willson TM, Herring LE, Graves LM, Baric RS. Investigation of the Host Kinome Response to Coronavirus Infection Reveals PI3K/mTOR Inhibitors as Betacoronavirus Antivirals. J Proteome Res. 2023 Oct 6;22(10):3159-3177. doi: 10.1021/acs.jproteome.3c00182. Epub 2023 Aug 27. PMID: 37634194.
  20. Liu C, Kutchukian P, Nguyen ND, AlQuraishi M, Sorger PK. A Hybrid Structure- Based Machine Learning Approach for Predicting Kinase Inhibition by Small Molecules. J Chem Inf Model. 2023 Sep 11;63(17):5457-5472. doi: 10.1021/acs.jcim.3c00347. Epub 2023 Aug 18. PMID: 37595065; PMCID: PMC10498990.
  21. Joisa CU, Chen KA, Beville S, Stuhlmiller T, Berginski ME, Okumu D, Golitz BT, Johnson GL, Gomez SM. Combined kinome inhibition states are predictive of cancer cell line sensitivity to kinase inhibitor combination therapies. bioRxiv [Preprint]. 2023 Aug 3:2023.08.01.551346. doi: 10.1101/2023.08.01.551346. Update in: Pac Symp Biocomput. 2024;29:276-290. PMID: 37577663; PMCID: PMC10418192.
  22. Castano A, Silvestre M, Wells CI, Sanderson JL, Ferrer CA, Ong HW, Lang Y, Richardson W, Silvaroli JA, Bashore FM, Smith JL, Genereux IM, Dempster K, Drewry DH, Pabla NS, Bullock AN, Benke TA, Ultanir SK, Axtman AD. Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin- dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology. Elife. 2023 Jul 25;12:e88206. doi: 10.7554/eLife.88206. PMID: 37490324; PMCID: PMC10406435.
  23. Flint AC, Mitchell DK, Angus SP, Smith AE, Bessler W, Jiang L, Mang H, Li X, Lu Q, Rodriguez B, Sandusky GE, Masters AR, Zhang C, Dang P, Koenig J, Johnson GL, Shen W, Liu J, Aggarwal A, Donoho GP, Willard MD, Bhagwat SV, Clapp DW, Rhodes SD. Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma. Clin Cancer Res. 2023 Sep 1;29(17):3438-3456. doi: 10.1158/1078-0432.CCR-22-2854. PMID: 37406085.
  24. Yang X, Ong HW, Dickmander RJ, Smith JL, Brown JW, Tao W, Chang E, Moorman NJ, Axtman AD, Willson TM. Optimization of 3-Cyano-7-cyclopropylamino- pyrazolo[1,5-a]pyrimidines Toward the Development of an In Vivo Chemical Probe for CSNK2A. bioRxiv [Preprint]. 2023 Jul 23:2023.05.15.540828. doi: 10.1101/2023.05.15.540828. Update in: ACS Omega. 2023 Oct 10;8(42):39546-39561. PMID: 37292607; PMCID: PMC10245575.
  25. Durcan TM, Axtman AD. Editorial: The next generation of tools and technologies for studying human neurons in a dish. Front Cell Neurosci. 2023 Apr 14;17:1196543. doi: 10.3389/fncel.2023.1196543. PMID: 37124399; PMCID: PMC10140577.
  26. Sahu I, Zhu H, Buhrlage SJ, Marto JA. Proteomic approaches to study ubiquitinomics. Biochim Biophys Acta Gene Regul Mech. 2023 Jun;1866(2):194940. doi: 10.1016/j.bbagrm.2023.194940. Epub 2023 Apr 29. PMID: 37121501; PMCID: PMC10612121.
  27. Ong HW, Liang Y, Richardson W, Lowry ER, Wells CI, Chen X, Silvestre M, Dempster K, Silvaroli JA, Smith JL, Wichterle H, Pabla NS, Ultanir SK, Bullock AN, Drewry DH, Axtman AD. Discovery of a Potent and Selective CDKL5/GSK3 Chemical Probe That Is Neuroprotective. ACS Chem Neurosci. 2023 May 3;14(9):1672-1685. doi: 10.1021/acschemneuro.3c00135. Epub 2023 Apr 21. PMID: 37084253; PMCID: PMC10161233.
  28. Davis-Gilbert ZW, Krämer A, Dunford JE, Howell S, Senbabaoglu F, Wells CI, Bashore FM, Havener TM, Smith JL, Hossain MA, Oppermann U, Drewry DH, Axtman AD. Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2. ACS Med Chem Lett. 2023 Mar 14;14(4):432-441. doi: 10.1021/acsmedchemlett.2c00530. PMID: 37077385; PMCID: PMC10108397.
  29. Bashore FM, Marquez AB, Chaikuad A, Howell S, Dunn AS, Beltran AA, Smith JL, Drewry DH, Beltran AS, Axtman AD. Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis. Sci Rep. 2023 Apr 14;13(1):6118. doi: 10.1038/s41598-023-32854-4. PMID: 37059819; PMCID: PMC10104807.
  30. Yang X, Smith JL, Beck MT, Wilkinson JM, Michaud A, Vasta JD, Robers MB, Willson TM. Development of Cell Permeable NanoBRET Probes for the Measurement of PLK1 Target Engagement in Live Cells. Molecules. 2023 Mar 25;28(7):2950. doi: 10.3390/molecules28072950. PMID: 37049713; PMCID: PMC10095950.
  31. Berginski ME, Joisa CU, Golitz BT, Gomez SM. Kinome inhibition states and multiomics data enable prediction of cell viability in diverse cancer types. PLoS Comput Biol. 2023 Feb 21;19(2):e1010888. doi: 10.1371/journal.pcbi.1010888. PMID: 36809237; PMCID: PMC9983880.
  32. Ong HW, Liang Y, Richardson W, Lowry ER, Wells CI, Chen X, Silvestre M, Dempster K, Silvaroli JA, Smith JL, Wichterle H, Pabla NS, Ultanir SK, Bullock AN, Drewry DH, Axtman AD. A Potent and Selective CDKL5/GSK3 Chemical Probe is Neuroprotective. bioRxiv [Preprint]. 2023 Feb 10:2023.02.09.527935. doi: 10.1101/2023.02.09.527935. Update in: ACS Chem Neurosci. 2023 Apr 21;: PMID: 36798313; PMCID: PMC9934649.
  33. Chan WC, Liu X, Magin RS, Girardi NM, Ficarro SB, Hu W, Tarazona Guzman MI, Starnbach CA, Felix A, Adelmant G, Varca AC, Hu B, Bratt AS, DaSilva E, Schauer NJ, Jaen Maisonet I, Dolen EK, Ayala AX, Marto JA, Buhrlage SJ. Accelerating inhibitor discovery for deubiquitinating enzymes. Nat Commun. 2023 Feb 8;14(1):686. doi: 10.1038/s41467-023-36246-0. PMID: 36754960; PMCID: PMC9908924.
  34. Wells C, Liang Y, Pulliam TL, Lin C, Awad D, Eduful B, O'Byrne S, Hossain MA, Catta-Preta CMC, Ramos PZ, Gileadi O, Gileadi C, Couñago RM, Stork B, Langendorf CG, Nay K, Oakhill JS, Mukherjee D, Racioppi L, Means AR, York B, McDonnell DP, Scott JW, Frigo DE, Drewry DH. SGC-CAMKK2-1: A Chemical Probe for CAMKK2. Cells. 2023 Jan 11;12(2):287. doi: 10.3390/cells12020287. PMID: 36672221; PMCID: PMC9856672.
  35. Johnson JL, Yaron TM, Huntsman EM, Kerelsky A, Song J, Regev A, Lin TY, Liberatore K, Cizin DM, Cohen BM, Vasan N, Ma Y, Krismer K, Robles JT, van de Kooij B, van Vlimmeren AE, Andrée-Busch N, Käufer NF, Dorovkov MV, Ryazanov AG, Takagi Y, Kastenhuber ER, Goncalves MD, Hopkins BD, Elemento O, Taatjes DJ, Maucuer A, Yamashita A, Degterev A, Uduman M, Lu J, Landry SD, Zhang B, Cossentino I, Linding R, Blenis J, Hornbeck PV, Turk BE, Yaffe MB, Cantley LC. An atlas of substrate specificities for the human serine/threonine kinome. Nature. 2023 Jan;613(7945):759-766. doi: 10.1038/s41586-022-05575-3. Epub 2023 Jan 11. PMID: 36631611; PMCID: PMC9876800.
  36. Mills CE, Subramanian K, Hafner M, Niepel M, Gerosa L, Chung M, Victor C, Gaudio B, Yapp C, Nirmal AJ, Clark N, Sorger PK. Multiplexed and reproducible high content screening of live and fixed cells using Dye Drop. Nat Commun. 2022 Nov 14;13(1):6918. doi: 10.1038/s41467-022-34536-7. PMID: 36376301; PMCID: PMC9663587.
  37. Drewry DH, Potjewyd FM, Bayati A, Smith JL, Dickmander RJ, Howell S, Taft- Benz S, Min SM, Hossain MA, Heise M, McPherson PS, Moorman NJ, Axtman AD. Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses. J Med Chem. 2022 Oct 13;65(19):12860-12882. doi: 10.1021/acs.jmedchem.2c00697. Epub 2022 Sep 16. PMID: 36111834; PMCID: PMC9574855.
  38. Mishra S, Kinoshita C, Axtman AD, Young JE. Evaluation of a Selective Chemical Probe Validates That CK2 Mediates Neuroinflammation in a Human Induced Pluripotent Stem Cell-Derived Microglial Model. Front Mol Neurosci. 2022 Jun 14;15:824956. doi: 10.3389/fnmol.2022.824956. Erratum in: Front Mol Neurosci. 2023 Nov 21;16:1334040. PMID: 35774866; PMCID: PMC9239073.
  39. Karim M, Saul S, Ghita L, Sahoo MK, Ye C, Bhalla N, Lo CW, Jin J, Park JG, Martinez-Gualda B, East MP, Johnson GL, Pinsky BA, Martinez-Sobrido L, Asquith CRM, Narayanan A, De Jonghe S, Einav S. Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies. Antiviral Res. 2022 Aug;204:105367. doi: 10.1016/j.antiviral.2022.105367. Epub 2022 Jun 20. PMID: 35738348; PMCID: PMC9212491.
  40. Tiek DM, Erdogdu B, Razaghi R, Jin L, Sadowski N, Alamillo-Ferrer C, Hogg JR, Haddad BR, Drewry DH, Wells CI, Pickett JE, Song X, Goenka A, Hu B, Goldlust SA, Zuercher WJ, Pertea M, Timp W, Cheng SY, Riggins RB. Temozolomide-induced guanine mutations create exploitable vulnerabilities of guanine-rich DNA and RNA regions in drug-resistant gliomas. Sci Adv. 2022 Jun 24;8(25):eabn3471. doi: 10.1126/sciadv.abn3471. Epub 2022 Jun 22. PMID: 35731869; PMCID: PMC9216507.
  41. Zhu H, Mellors JS, Chan WC, Thompson JW, Ficarro SB, Tavares I, Bratt AS, Decker J, Krause M, Kruppa G, Buhrlage SJ, Marto JA. On-Chip Preconcentration Microchip Capillary Electrophoresis Based CE-PRM-LIVE for High-Throughput Selectivity Profiling of Deubiquitinase Inhibitors. Anal Chem. 2022 Jul 12;94(27):9508-9513. doi: 10.1021/acs.analchem.2c01337. Epub 2022 Jun 21. PMID: 35729701; PMCID: PMC10654755.
  42. Yang X, Dickmander RJ, Bayati A, Taft-Benz SA, Smith JL, Wells CI, Madden EA, Brown JW, Lenarcic EM, Yount BL Jr, Chang E, Axtman AD, Baric RS, Heise MT, McPherson PS, Moorman NJ, Willson TM. Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses. ACS Chem Biol. 2022 Jul 15;17(7):1937-1950. doi: 10.1021/acschembio.2c00378. Epub 2022 Jun 19. PMID: 35723434; PMCID: PMC9236220.
  43. Ficarro SB, Max Alexander W, Tavares I, Marto JA. Open source fraction collector/MALDI spotter for proteomics. HardwareX. 2022 Apr 18;11:e00305. doi: 10.1016/j.ohx.2022.e00305. PMID: 35518277; PMCID: PMC9062586.
  44. Agajanian MJ, Potjewyd FM, Bowman BM, Solomon S, LaPak KM, Bhatt DP, Smith JL, Goldfarb D, Axtman AD, Major MB. Protein proximity networks and functional evaluation of the casein kinase 1 gamma family reveal unique roles for CK1γ3 in WNT signaling. J Biol Chem. 2022 Jun;298(6):101986. doi: 10.1016/j.jbc.2022.101986. Epub 2022 Apr 27. PMID: 35487243; PMCID: PMC9157009.
  45. Asquith CRM, Temme L, East MP, Laitinen T, Pickett J, Kwarcinski FE, Sinha P, Wells CI, Johnson GL, Zutshi R, Drewry DH. Identification of 4-Anilinoquin(az)oline as a Cell-Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype. ChemMedChem. 2022 Jun 20;17(12):e202200161. doi: 10.1002/cmdc.202200161. Epub 2022 May 9. PMID: 35403825; PMCID: PMC9233141.
  46. Kirchoff KE, Gomez SM. EMBER: multi-label prediction of kinase-substrate phosphorylation events through deep learning. Bioinformatics. 2022 Apr 12;38(8):2119-2126. doi: 10.1093/bioinformatics/btac083. PMID: 35157015; PMCID: PMC9004653.
  47. Yang X, Dickmander RJ, Bayati A, Taft-Benz SA, Smith JL, Wells CI, Madden EA, Brown JW, Lenarcic EM, Yount BL Jr, Chang E, Axtman AD, Baric RS, Heise MT, McPherson PS, Moorman NJ, Willson TM. Host kinase CSNK2 is a target for inhibition of pathogenic β-coronaviruses including SARS-CoV-2. bioRxiv [Preprint]. 2022 Jan 26:2022.01.03.474779. doi: 10.1101/2022.01.03.474779. Update in: ACS Chem Biol. 2022 Jun 19;: PMID: 35018375; PMCID: PMC8750650.
  48. East MP, Johnson GL. Adaptive chromatin remodeling and transcriptional changes of the functional kinome in tumor cells in response to targeted kinase inhibition. J Biol Chem. 2022 Feb;298(2):101525. doi: 10.1016/j.jbc.2021.101525. Epub 2021 Dec 24. PMID: 34958800; PMCID: PMC8888345.
  49. Zhu H, Ficarro SB, Alexander WM, Fleming LE, Adelmant G, Zhang T, Willetts M, Decker J, Brehmer S, Krause M, East MP, Gray NS, Johnson GL, Kruppa G, Marto JA. PRM-LIVE with Trapped Ion Mobility Spectrometry and Its Application in Selectivity Profiling of Kinase Inhibitors. Anal Chem. 2021 Oct 19;93(41):13791-13799. doi: 10.1021/acs.analchem.1c02349. Epub 2021 Oct 4. PMID: 34606255; PMCID: PMC9297317.
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  51. Schirmer AU, Driver LM, Zhao MT, Wells CI, Pickett JE, O'Bryne SN, Eduful BJ, Yang X, Howard L, You S, Devi GR, DiGiovanni J, Freedland SJ, Chi JT, Drewry DH, Macias E. Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer. Mol Ther. 2022 Jan 5;30(1):485-500. doi: 10.1016/j.ymthe.2021.08.029. Epub 2021 Aug 25. PMID: 34450249; PMCID: PMC8753456.
  52. Drewry DH, Annor-Gyamfi JK, Wells CI, Pickett JE, Dederer V, Preuss F, Mathea S, Axtman AD. Identification of Pyrimidine-Based Lead Compounds for Understudied Kinases Implicated in Driving Neurodegeneration. J Med Chem. 2022 Jan 27;65(2):1313-1328. doi: 10.1021/acs.jmedchem.1c00440. Epub 2021 Aug 1. PMID: 34333981; PMCID: PMC8802302.
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