The Impact of Assay Design on Medicinal Chemistry: Case Studies

1. Gilliland, C. T., White, J., Gee, B., et al. The Fundamental Characteristics of a Translational Scientist. ACS Pharmacol. Transl. Sci. 2019, 2, 213–216.
Google Scholar | Crossref | Medline2. Khanna, R., Benjamin, E. R., Pellegrino, L., et al. The Pharmacological Chaperone Isofagomine Increases the Activity of the Gaucher Disease L444P Mutant form of β-Glucosidase. FEBS J. 2010, 277, 1618–1638.
Google Scholar | Crossref | Medline3. Zheng, W., Padia, J., Urban, D. J., et al. Three Classes of Glucocerebrosidase Inhibitors Identified by Quantitative High-Throughput Screening Are Chaperone Leads for Gaucher Disease. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 13192–13197.
Google Scholar | Crossref | Medline4. Goldin, E., Zheng, W., Motabar, O., et al. High Throughput Screening for Small Molecule Therapy for Gaucher Disease Using Patient Tissue as the Source of Mutant Glucocerebrosidase. PLoS One 2012, 7, e29861.
Google Scholar | Crossref5. Marugan, J. J., Zheng, W., Motabar, O., et al. Evaluation of Quinazoline Analogues as Glucocerebrosidase Inhibitors with Chaperone Activity. J. Med. Chem. 2011, 54, 1033–1058.
Google Scholar | Crossref | Medline6. Marugan, J. J., Huang, W., Motabar, O., et al. Non-Iminosugar Glucocerebrosidase Small Molecule Chaperones. Med. Chem. Comm. 2012, 3, 56–60.
Google Scholar | Crossref7. Aflaki, E., Stubblefield, B. K., Maniwang, E., et al. Macrophage Models of Gaucher Disease for Evaluating Disease Pathogenesis and Candidate Drugs. Sci. Transl. Med. 2014, 6, 240ra73–240ra73.
Google Scholar | Crossref | Medline8. Aflaki, E., Borger, D. K., Moaven, N., et al. A New Glucocerebrosidase Chaperone Reduces α-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism. J. Neurosci. 2016, 36, 7441–7452.
Google Scholar | Crossref | Medline9. Mazzulli, J. R., Zunke, F., Tsunemi, T., et al. Activation of β-Glucocerebrosidase Reduces Pathological α-Synuclein and Restores Lysosomal Function in Parkinson’s Patient Midbrain Neurons. J. Neurosci. 2016, 36, 7693–7706.
Google Scholar | Crossref | Medline10. Patnaik, S., Zheng, W., Choi, J. H., et al. Discovery, Structure–Activity Relationship, and Biological Evaluation of Noninhibitory Small Molecule Chaperones of Glucocerebrosidase. J. Med. Chem. 2012, 55, 5734–5748.
Google Scholar | Crossref | Medline11. Roskoski, R. Properties of FDA-Approved Small Molecule Protein Kinase Inhibitors: A 2020 Update. Pharmacol. Res. 2020, 152, 104609.
Google Scholar | Crossref | Medline12. Bournez, C., Carles, F., Peyrat, G., et al. Comparative Assessment of Protein Kinase Inhibitors in Public Databases and in PKIDB. Molecules 2020, 25, 3226.
Google Scholar | Crossref13. LOPAC®1280—The Library of Pharmacologically Active Compounds . https://www.sigmaaldrich.com/life-science/cell-biology/bioactive-small-molecules/lopac1280-navigator.html (accessed 2021-01-21).
Google Scholar14. Sarathy, A., Wuebbles, R. D., Fontelonga, T. M., et al. SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy. Mol. Ther. 2017, 25, 1395–1407.
Google Scholar | Crossref | Medline15. Anastassiadis, T., Deacon, S. W., Devarajan, K., et al. Comprehensive Assay of Kinase Catalytic Activity Reveals Features of Kinase Inhibitor Selectivity. Nat. Biotechnol. 2011, 29, 1039–1045.
Google Scholar | Crossref | Medline16. Patricelli, M. P., Nomanbhoy, T. K., Wu, J., et al. In Situ Kinase Profiling Reveals Functionally Relevant Properties of Native Kinases. Chem. Biol. 2011, 18, 699–710.
Google Scholar | Crossref | Medline17. Klaeger, S., Heinzlmeir, S., Wilhelm, M., et al. The Target Landscape of Clinical Kinase Drugs. Science 2017, 358, eaan4368.
Google Scholar | Crossref | Medline18. Reinecke, M., Heinzlmeir, S., Wilhelm, M., et al. Kinobeads: A Chemical Proteomic Approach for Kinase Inhibitor Selectivity Profiling and Target Discovery. In Target Discovery and Validation; Plowright AT, Ed.; Wiley, 2019; pp 97–130.
Google Scholar | Crossref19. Tsai, J., Lee, J. T., Wang, W., et al. Discovery of a Selective Inhibitor of Oncogenic B-Raf Kinase with Potent Antimelanoma Activity. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 3041–3046.
Google Scholar | Crossref | Medline20. Bollag, G., Hirth, P., Tsai, J., et al. Clinical Efficacy of a RAF Inhibitor Needs Broad Target Blockade in BRAF-Mutant Melanoma. Nature 2010, 467, 596–599.
Google Scholar | Crossref | Medline21. Yang, H., Higgins, B., Kolinsky, K., et al. RG7204 (PLX4032), a Selective BRAFV600E Inhibitor, Displays Potent Antitumor Activity in Preclinical Melanoma Models. Cancer Res. 2010, 70, 5518–5527.
Google Scholar | Crossref | Medline22. Savitski, M. M., Reinhard, F. B., Franken, H., et al. Tracking Cancer Drugs in Living Cells by Thermal Profiling of the Proteome. Science 2014, 346, 1255784.
Google Scholar | Crossref | Medline23. Wu, C. K., Dailey, H. A., Rose, J. P., et al. The 2.0 A Structure of Human Ferrochelatase, the Terminal Enzyme of Heme Biosynthesis. Nat. Struct. Biol. 2001, 8, 156–160.
Google Scholar | Crossref | Medline24. Klaeger, S., Gohlke, B., Perrin, J., et al. Chemical Proteomics Reveals Ferrochelatase as a Common Off-Target of Kinase Inhibitors. ACS Chem. Biol. 2016, 11, 1245–1254.
Google Scholar | Crossref | Medline25. Cravatt, B. F., Wright, A. T., Kozarich, J. W. Activity-Based Protein Profiling: From Enzyme Chemistry to Proteomic Chemistry. Annu. Rev. Biochem. 2008, 77, 383–414.
Google Scholar | Crossref | Medline26. Karran, E., Mercken, M., De Strooper, B. The Amyloid Cascade Hypothesis for Alzheimer’s Disease: An Appraisal for the Development of Therapeutics. Nat. Rev Drug Discov. 2011, 10, 698–712.
Google Scholar | Crossref | Medline27. May, P. C., Dean, R. A., Lowe, S. L., et al. Robust Central Reduction of Amyloid-β in Humans with an Orally Available, Non-Peptidic β-Secretase Inhibitor. J. Neurosci. 2011, 31, 16507–16516.
Google Scholar | Crossref | Medline28. Fielden, M. R., Werner, J., Jamison, J. A., et al. Retinal Toxicity Induced by a Novel β-secretase Inhibitor in the Sprague-Dawley Rat. Toxicol. Pathol. 2015, 43, 581–592.
Google Scholar | SAGE Journals29. Brodney, M. A., Beck, E. M., Butler, C. R., et al. Utilizing Structures of CYP2D6 and BACE1 Complexes to Reduce Risk of Drug–Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors. J. Med. Chem. 2015, 58, 3223–3252.
Google Scholar | Crossref | Medline30. Mecklenburg, L., Schraermeyer, U. An Overview on the Toxic Morphological Changes in the Retinal Pigment Epithelium after Systemic Compound Administration. Toxicol. Pathol. 2007, 35, 252–267.
Google Scholar | SAGE Journals31. Roberds, S. L., Anderson, J., Basi, G., et al. BACE Knockout Mice Are Healthy Despite Lacking the Primary β-Secretase Activity in Brain: Implications for Alzheimer’s Disease Therapeutics. Hum. Mol. Genet. 2001, 10, 1317–1324.
Google Scholar | Crossref | Medline32. Koike, M., Nakanishi, H., Saftig, P., et al. Cathepsin D Deficiency Induces Lysosomal Storage with Ceroid Lipofuscin in Mouse CNS Neurons. J. Neurosci. 2000, 20, 6898–6906.
Google Scholar | Crossref | Medline33. Tyynelä, J., Sohar, I., Sleat, D. E., et al. A Mutation in the Ovine Cathepsin D Gene Causes a Congenital Lysosomal Storage Disease with Profound Neurodegeneration. EMBO J. 2000, 19, 2786–2792.
Google Scholar | Crossref | Medline34. Steinfeld, R., Reinhardt, K., Schreiber, K., et al. Cathepsin D Deficiency Is Associated with a Human Neurodegenerative Disorder. Am. J. Hum. Genet. 2006, 78, 988–998.
Google Scholar | Crossref | Medline35. Dineen, T. A., Chen, K., Cheng, A. C., et al. Inhibitors of β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1): Identification of (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5’H-spiro[chromeno[2,3-b]pyridine-5,4’-oxazol]-2’-amine (AMG-8718). J. Med. Chem. 2014, 57, 9811–9831.
Google Scholar | Crossref | Medline36. Yang, H. C., Chai, X., Mosior, M., et al. Biochemical and Kinetic Characterization of BACE1: Investigation into the Putative Species-Specificity for Beta- and Beta’-Cleavage Sites by Human and Murine BACE1. J. Neurochem. 2004, 91, 1249–1259.
Google Scholar | Crossref | Medline37. Tung, C. H., Bredow, S., Mahmood, U., et al. Preparation of a cathepsin D Sensitive Near-Infrared Fluorescence Probe for Imaging. Bioconjug. Chem. 1999, 10, 892–896.
Google Scholar | Crossref | Medline38. Chen, C.-S., Chen, W.-N., Zhou, M., et al. Probing the Cathepsin D Using a BODIPY FL-Pepstatin A: Applications in Fluorescence Polarization and Microscopy. J. Biochem. Biophys. Methods 2000, 42, 137–151.
Google Scholar | Crossref | Medline39. Zuhl, A. M., Nolan, C. E., Brodney, M. A., et al. Chemoproteomic Profiling Reveals That Cathepsin D Off-Target Activity Drives Ocular Toxicity of β-secretase inhibitors. Nat. Commun. 2016, 7, 13042.
Google Scholar | Crossref | Medline40. Mann, M. Functional and Quantitative Proteomics Using SILAC. Nat. Rev. Mol. Cell Biol. 2006, 7, 952–958.
Google Scholar | Crossref | Medline41. Harrison, R. K. Phase II and Phase III Failures: 2013–2015. Nat. Rev. Drug Discov. 2016, 15, 817–818.
Google Scholar | Crossref | Medline42. Force, T., Kolaja, K. L. Cardiotoxicity of Kinase Inhibitors: The Prediction and Translation of Preclinical Models to Clinical Outcomes. Nat. Rev. Drug Discov. 2011, 10, 111–126.
Google Scholar | Crossref | Medline43. Lin, A., Giuliano, C. J., Sayles, N. M., et al. CRISPR/Cas9 Mutagenesis Invalidates a Putative Cancer Dependency Targeted in On-Going Clinical Trials. eLife 2017, 6.
Google Scholar44. Sportsman, J. R., Gaudet, E. A., Boge, A. Immobilized Metal Ion Affinity-Based Fluorescence Polarization (IMAP): Advances in Kinase Screening. Assay Drug Dev. Technol. 2004, 2, 205–214.
Google Scholar | Crossref | Medline45. Cho, Y.-S., Kang, Y., Kim, K., et al. The Crystal Structure of MPK38 in Complex with OTSSP167, an Orally Administrative MELK Selective Inhibitor. Biochem. Biophys. Res. Commun. 2014, 447, 7–11.
Google Scholar | Crossref | Medline46. Lin, A., Giuliano, C. J., Palladino, A., et al. Off-Target Toxicity Is a Common Mechanism of Action of Cancer Drugs Undergoing Clinical Trials. Sci. Transl. Med. 2019, 11, eaaw8412.
Google Scholar | Crossref47. Welch, E. M., Barton, E. R., Zhuo, J., et al. PTC124 Targets Genetic Disorders Caused by Nonsense Mutations. Nature 2007, 447, 87–91.
Google Scholar | Crossref | Medline48. Thorne, N., Inglese, J., Auld, D. S. Illuminating Insights into Firefly Luciferase and Other Bioluminescent Reporters Used in Chemical Biology. Chem. Biol. 2010, 17, 646–657.
Google Scholar | Crossref | Medline49. Auld, D. S., Thorne, N., Maguire, W. F., et al. Mechanism of PTC124 Activity in Cell-Based Luciferase Assays of Nonsense Codon Suppression. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 3585–3590.
Google Scholar | Crossref | Medline50. Peltz, S. W., Welch, E. M., Jacobson, A., et al. Nonsense Suppression Activity of PTC124 (ataluren). Proc. Natl. Acad. Sci. U.S.A. 2009, 106, E64–E65.
Google Scholar | Crossref | Medline51. Auld, D. S., Lovell, S., Thorne, N., et al. Molecular Basis for the High-Affinity Binding and Stabilization of Firefly Luciferase by PTC124. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 4878–4883.

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