Adrian Sheldon is the Director of the In Vitro ADME group at Charles River's Discovery site in Worcester, Massachusetts where he leads a team of assay and bioanalytical scientists who characterize potential drug molecules.
Dr. Sheldon has been in drug research and development for over 29 years, working at several biotechnology and contract research companies. Prior to joining Charles River in 2002 to establish the in vitro ADME services in Massachusetts, he worked as a Group Leader and Senior Investigator at ArQule (acquired by Merck) in Woburn, MA, and as a Senior Scientist at OsteoArthritis Sciences in Cambridge, MA.
Dr. Sheldon received his AB degree from Harvard University and his PhD in Physiology and Cell Biology from Boston University. He has co-authored 37 papers and abstracts and is a co-inventor of two US patents.
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Publications/Posters
Meloche, S., Amin, J. and Sheldon, A. (2019) Evaluation of Single-Use Rapid Equilibrium Dialysis (RED) Device for Automated Octanol-Water Partitioning (LogD7.4) Assay to Assess the Lipophilicity of Drug Compounds. Poster presented at ISSX conference, July 2019.
Amin, J., Plourde, D. Lewia, A., Walton, P., Powell, F., Patel, G., Dearborn, S. and Sheldon, A. (2018) Using Statistical Analyses to Demonstrate Equivalency Between Automated and Manual Processes to Deliver High Quality In Vitro ADME Data Even Faster. Poster presented at ISSX conference, July 2018.
Dearborn, S., Walton, P., Patel, G., Stedman, J. and Sheldon, A. (2016) Characterization of a Rapid and Sensitive Method for Determination of Melanin Binding by Drugs (Parent and Metabolite). Poster presented at AAPS conference, November 2016.
Wachtel, D., Tobin, J., Virasingh, B., Sheldon, A., Dearborn, S., Guo, Y., Germano, P. Forsyth, S. and Ribadeneira, M. (2016) A 10-Point Time Course Pharmacokinetic Study Collected from a Single Mouse by use of the Mitra Microsampling Devices. Poster presented at ASMS conference, June 2016.
Lewia, A., Ye, G. and Sheldon, A. (2016) Use of Ultracentrifugation to Determine Protein Binding of Compounds Unstable in Matrix. Poster presented at AAPS-NBC conference, May 2016; poster T2069.
Patel, G.,Dearborn, S., Stedman, J., Rivera, J. and Sheldon, A. (2016) Use of Co-Spikes and Compound Cassetting to Assess Functional Integrity of Caco-2 Monolayers and Increase Throughput. Poster presented at AAPS Transporters Workshop, April 2016.
Lee, K.C., Shorr, R., Rodriguez, R., Maturo, C., Boteju, L.W. and Sheldon, A. (2011) Formation and Anti-Tumor Activity of Uncommon In Vitro and In Vivo Metabolites of CPI-613, a Novel Anti-Tumor Compound That Selectively Alters Tumor Energy Metabolism. Drug Metab. Lett. 5, 163-182.
Shen, A.Q., Sheldon, A., Pietrasiewicz, A. and Zhang, X. (2010) The Challenges of LC/MS/MS Quantitative Analysis of Cytarabine Analogs and Variable Endogenous Interferences in Different Species. Poster presented at AAPS conference, November 2010.
Sheldon, A., Shen, A., Nguyen, T. and Zhang, X. (2009) Highly Bound Drugs May Need Longer Dialysis Times to Achieve Equilibrium in Plasma Protein Binding Assays. Drug Metab. Rev. 41, 122; poster presented at 16th International ISSX conference, October 2009.
Liu, S., Dearborn, S., Mitchell, S., Walton, P. and Sheldon, A. (2008) In Vitro Identification and Quantification of 6 Novel Phase I / Phase II Metabolites of Galangin Using Human Liver S9. Poster presented at ASMS conference, June 2008.
Liu, S., Haspel, H.C., Mitchell, S., Zhang, X., Liu, H., Yang, J. and Sheldon, A. (2007) In Vitro Assessment of Phase I and II Butoconazole Metabolites from Multiple Species Using a Novel 2D Image Comparison Method. Poster presented at ASMS conference, June 2007.
Haspel, H. C., Walton, P., Campbell, R., Mitchell, S., Zhang, X., Liu, S, and Sheldon, A. (2006) Binding of Phosphodiesterase Type 5 Inhibitors Sildenafil, Tadalafil, and Vardenafil to Total Human Plasma Proteins and Human Serum Albumin (HSA) and 1-Acid Glycoprotein (AGP). Poster presented at 9th International ISSX conference; also presented at the New England Drug Metabolism Discussion Group conference, June 2006.
Haspel, H. C., Liu, S., Mitchell, S., Zhang, X., Liu, H., Yang, J. and Sheldon, A. (2006) In Vitro Profiling of Phase I and Phase II Metabolites of Butoconazole from Multiple Species. Poster presented at 9th International ISSX conference.
Haspel, H. C., Bowman, K., Mitchell, S., Walton, P. and Sheldon, A. (2005) High Throughput Filter Plate-Based Melanin Binding Assay. Drug Metab. Rev. 37, 286 (poster presented at 8th International ISSX conference). Poster also presented at the World Pharmaceutical Congress, May 2005.
Sheldon, A., Mitchell, S., Bowman, K. and Haspel, H. C. (2004) Validation of an Automated Rubidium Flux-Based Method for hERG Channel Inhibition Screening. Drug Metab. Rev. 36, 228 (poster presented at 7th International ISSX conference).
Haspel, H. C., Bowman, K., Mitchell, S. and Sheldon, A. (2004) High Throughput Equilibrium Dialysis-Based Drug Plasma Protein Binding Assay. Drug Metab. Rev. 36, 248 (poster presented at 7th International ISSX conference).
(Nov. 2003) Pharmacokinetic Studies: The Earlier the Better; In House or Contract Out? Drug Discovery and Development (interviewed for article).
Haspel, H., Walton, P. and Sheldon, A. (2003) Automated and High Throughput Assay for Drug Binding to Human Serum Albumin and Alpha-1 Acid Glycoprotein: Multiplexing Displacement of Fluorescent Probes and Quenching of Intrinsic Tryptophan Fluorescence. Poster presented at Sept. 2003 9th Annual SBS conference.
Hardy, L., Gallion, S. and Sheldon, A. (Jan. 2002) Tilting Toward Targets: Design of Biased Compound Libraries for Ion Channels. Current Drug Discovery, 25-27.
Gustafson, G.R., Baldino, C.M., O’Donnell, M.M.E., Sheldon, A., Tarsa, R.J., Verni, C.V. and Coffen, D.L. (1998) Incorporation of Carbohydrates and Peptides into Large Triazine-Based Screening Libraries Using Automated Parallel Synthesis. Tetrahedron 54, 4051-4065.
Sheldon, A., Chipman, S., Petracca, J., Caserta, J., Werner, C., Casebier, D. and Hogan, J. (1997) The Integration of Parallel Combinatorial Unit Chemical Synthesis and Multiplexed, High Throughput Screening to Accelerate Drug Discovery. Society for Biomolecular Screening 3rd Meeting (September, 1997; poster abstract).
Sheldon, A. and Chen, J.M. (1996) Annexin/Protein Interactions: Clues for Function. In, Annexins: Molecular Structure to Cellular Function (Seaton, B.A., ed.), pp. 133-141. R.G. Landes Co., Austin, TX.
Chen, J.M., Sheldon, A. and Pincus, M.R. (1995) Three-Dimensional Energy-Minimized Model of Human Type II “Smith” Collagen Microfibril. J. Biomol. Struct. Dyn. 12, 1129-1159.
Yeh, L.-A., Augustine, A.J., Lee, P., Riviere, L.R. and Sheldon, A. (1995) Interleukin-4, an Inhibitor of Cartilage Breakdown in Bovine Articular Cartilage Explants. J. Rheum. 22, 1740-1746.
Todhunter, R.J., Yeh, L.-A., Sheldon, A., Grisanzio, L., Walker, S., Burton-Wurster, N. and Lust, G. (1995) Effects of Stromelysin Activity on Proteoglycan Degradation of Canine Articular Cartilage Explants. Am. J. Vet. Res. 56, 1241-1247.
Chen, J.M. and Sheldon, A. (1994) A Three-Dimensional Energy-Minimized Model of the Human Type II “Smith” Collagen Microfibril. In, ACS Molecular Modeling Symposium Series 576 (Kumosinski, T.F. and Liebman, M.N., eds.). Amer. Chem. Soc., Washington, D.C., pp. 139-170.
Chen, J.M., Sheldon, A. and Pincus, M.R. (1993) Structure-Function Correlations of Calcium Binding and Calcium Channel Activities Based on 3-Dimensional Models of Human Annexins I, I, III, V and VII. J. Biomol. Struct. Dyn. 10, 1067-1089.
Sheldon, A., Booth, F.W. and Kirby, C.R. (1993) cAMP Levels in Fast-Twitch and Slow-Twitch Skeletal Muscle After an Acute Bout of Aerobic Exercise. AM. J. Physiol. 264, C1500-C1504.
Kirby, C.R., Sheldon, A. and Booth, F.W. (1992) Isolation and Infection of Rat Skeletal Muscle Satellite Cells for Retroviral-Mediated Gene Transfer. J. Cell. Biochem. 16F, 60 (abstract).
Hazarika, P., Kaetzel, M.A., Sheldon, A., Karin, N.J., Fleischer, S., Nelson, T.E. and Dedman, J.R. (1991) Annexin VI is Associated with Calcium-Sequestering Organelles. J. Cell. Biochem. 46, 78-85.
Hazarika, P., Sheldon, A., Kaetzel, M.A., Diaz-Munoz, M., Hamilton, S.L. and Dedman, J.R. (1991) Regulation of the Sarcoplasmic Reticulum Ca2+-Release Channel Requires Intact Annexin VI. J. Cell. Biochem. 46, 86-93.
Jong, Y.-J., Sheldon, A., Zhang, G.H. and Kraus-Friedmann, N. (1990) Purification of the Microsomal Ca2+-ATPase from Rat Liver. J. Membr. Biol. 118, 49-53.
Head, J.F. and Sheldon, A. (1990) Calcium-Binding Proteins in Squid Nervous Tissue. In, Stimulus-Response Coupling: The Role of Intracellular Calcium-Binding Proteins (Smith, V.L. and Dedman, J.R., eds.). CRC Press, Boca Raton, FL, pp. 109-132.
Sheldon, A. and Head, J.F. (1988) Calcium-Binding Properties of Two High Affinity Calcium-Binding Proteins from Squid Optic Lobe. J. Biol. Chem. 263, 14384-14389.
Sheldon, A. and Head, J.F. (1987) Studies on Two High-Affinity, Calcium-Binding Proteins in Squid Optic Lobe. In, Calcium-Binding Proteins in Health and Disease (Norman, A.W. et al., eds.). New York: Academic Press, pp. 418-420.
Lehman, W., Sheldon, A. and Madonia, W. (1987) Diversity in Smooth Muscle Thin Filament Composition. Biochim. Biophys. Acta 914, 35-39.
Lenz, J., Crowther, R., Klimenko, S., Sheldon, A., Elfassi, E. and Haseltine, W. (1982) Leukemogenic Determinants of the SL3-3 Virus. RNA Tumor Viruses meeting (May, 1982), Cold Spring Harbor Laboratory, p. 208 (abstract).
Presentations
Solvo Meet-the-Experts Transporter Workshop, Cambridge, MA (05-Sep-2019). Approaches and Lessons Learned in Establishing HT-ADME Assays.
A Journey into Drug Discovery and Development Workshop, Mount Sinai School of Medicine, NY (26-Sep-2018). Lead Development and in vitro ADME considerations for Drug Discovery.
Ohio State University Drug Development Institute (28-Mar-2017). In Vitro ADMET Considerations for Drug Discovery and Lead Generation.
Maryland Technology Development Center (01-Sep-2005). Benefits of Early In Vitro ADMET Testing to the Drug Discovery Process.
GPC Biotech, Inc. (17-Sep-2003). Benefits of In Vitro ADMET Data.
LRIG (Laboratory Robotics Interest Group) meeting (2000). Enabling Parallel Optimization Using High Throughput ADMET and Library Profiling.
The Society for Biomolecular Screening 5th meeting (April, 1999). Strategies for Integrating High-Throughput Chemical Synthesis and Biological Screening to Accelerate Lead Discovery: Chemotype Profiling, Subset Sampling, and Pharmacological HTS.
The Society for Biomolecular Screening 4th meeting (May, 1998). The Integration of Spatially Addressable Parallel Chemical Synthesis and Multiplexed High Throughput Bioassays to Accelerate Lead Generation and Optimization.
Patents
Brinner, K.M., Coffen, D.L., Goetzinger, W.K., Kyranos, J.N., Powers, D.G., Sheldon, A. (1998) U.S. Patent Application 60/077,799: Protease Inhibitors. Filed 12 March, 1998.
Yeh, L.-A., Augustine, A.J. and Sheldon, A. (1997) U.S. Patent # 5,679,338: Use of Interleukin-4 for Inhibition of the Breakdown of Articular Cartilage and Other Tissues.