210 Washtenaw Avenue
Ann Arbor, MI 48109-2216
Available to mentor
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Postdoctoral FellowUniversity of Michigan, Biophysics Research Division, 1996
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Ph.D.Wayne State University, Detroit, MI, 1992
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B.A.University of Findlay, Findlay, Ohio, 1986
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Center MemberRogel Cancer Center
Structure-based drug design: We utilize X-ray crystallography in conjunction with various biophysical techniques (DSF, ITC, DSC, BLI and LS-MS) to elucidate the binding modes of ligands to their target proteins and optimize small molecule compounds into clinical leads. Our efforts led to the development of an FDA approved drug against XIAP marketed by Merck as Xevinapant to treat locally advanced squamous cell carcinoma of the head and neck.
High-Throughput Screening: We refine proteins into stable, soluble targets that can be studied in vitro, then perform target screening against billions of compounds employing DNA-encoded libraries or several thousand chemical fragments using differential scanning fluorimetry to identify chemical matter (hits) that can be developed into lead compounds.
Metal chelation in proteins: We use de novo protein design to engineer different metal sites into three-stranded coil-coils to replicate active sites of metalloenzymes.
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Cárdenas EL, O'Rourke RL, Menon A, Vega-Hernández G, Meagher J, Stuckey J, Garner AL. bioRxiv, 2024 Sep 27;Journal ArticleSecond-Generation Cap Analogue Prodrugs for Targeting Aberrant Eukaryotic Translation Initiation Factor 4E (eIF4E) Activity in Drug-Resistant Melanoma.
DOI:10.1101/2024.09.25.614990 PMID: 39386734 -
Yuan T, Kumar S, Skinner ME, Victor-Joseph R, Abuaita M, Keijer J, Zhang J, Kunkel TJ, Liu Y, Petrunak EM, Saunders TL, Lieberman AP, Stuckey JA, Neamati N, Al-Murshedi F, Alfadhel M, Spelbrink JN, Rodenburg R, de Boer VCJ, Lombard DB. iScience, 2024 Jun 21; 27 (6): 109991Journal ArticleHuman SIRT5 variants with reduced stability and activity do not cause neuropathology in mice.
DOI:10.1016/j.isci.2024.109991 PMID: 38846003 -
Yuan X, Sabzvar MK, Patil AD, Chinnaswamy K, Howie KL, Andhavaram R, Wang B, Siegler MA, Dumaz A, Stuckey JA, Corey SJ, Maciejewski JP, Visconte V, Yang C-Y. Res Sq, 2024 Jun 3;Journal ArticleComprehensive Analyses of the Effects of the Small-Molecule Inhibitor of the UHM Domain in the Splicing Factor U2AF1 in Leukemia Cells.
DOI:10.21203/rs.3.rs-4477663/v1 PMID: 38883705 -
Kaneshige A, Yang Y, Bai L, Wang M, Xu R, Mallik L, Chinnaswamy K, Metwally H, Wang Y, McEachern D, Tošović J, Yang C-Y, Kirchhoff PD, Meagher JL, Stuckey JA, Wang S. J Med Chem, 2024 Sep 23;Journal ArticleDiscovery of AK-1690: A Potent and Highly Selective STAT6 PROTAC Degrader.
DOI:10.1021/acs.jmedchem.4c01009 PMID: 39311434 -
Xu R, Zhou H, Bai L, McEachern D, Wu D, Acharyya RK, Wang M, Tošović J, Yang C-Y, Chinnaswamy K, Meagher JL, Stuckey JA, Liu C, Wang M, Wen B, Sun D, Wang S. J Med Chem, 2024 Nov 7;Journal ArticleDiscovery of SD-436: A Potent, Highly Selective and Efficacious STAT3 PROTAC Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression.
DOI:10.1021/acs.jmedchem.4c01946 PMID: 39509603 -
Yuan X, Jiang H, Fu D, Rech JC, Robida A, Rajanayake K, Yuan H, He M, Wen B, Sun D, Liu C, Chinnaswamy K, Stuckey JA, Paczesny S, Yang C-Y. ACS Pharmacol Transl Sci, 2023 Sep 8; 6 (9): 1275 - 1287.Journal ArticleProphylactic Mitigation of Acute Graft versus Host Disease by Novel 2-(Pyrrolidin-1-ylmethyl)pyrrole-Based Stimulation-2 (ST2) Inhibitors.
DOI:10.1021/acsptsci.3c00122 PMID: 37705593 -
Cárdenas EL, O'Rourke RL, Menon A, Meagher J, Stuckey J, Garner AL. J Med Chem, 2023 Aug 10; 66 (15): 10734 - 10745.Journal ArticleDesign of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.
DOI:10.1021/acs.jmedchem.3c00917 PMID: 37471629 -
Hu J, Hu B, Xu F, Wang M, Qin C, McEachern D, Stuckey J, Wang S. J Med Chem, 2023 Jun 22; 66 (12): 8222 - 8237.Journal ArticlePrecise Conformational Control Yielding Highly Potent and Exceptionally Selective BRD4 Degraders with Strong Antitumor Activity.
DOI:10.1021/acs.jmedchem.3c00520 PMID: 37289649
