Lead Discovery Targets Using Label-free Screening of Native Substrates


Here is a list of more than 55 peer-reviewed published references using the RapidFire MS system (platform we use for your label-free screening projects). Links to the PubMed source are provided as well.

  1. Veach BT, Mudalige TK, Rye P. (2017) RapidFire Mass Spectrometry with Enhanced Throughput as an Alternative to Liquid-Liquid Salt Assisted Extraction and LC/MS Analysis for Sulfonamides in Honey. Analytical Chemistry 2017 Mar 2 Epub ahead of print
  2. X Zhang, M Romm, X Zheng, EM Zinka, Y-M Kim, KE Burnum-Johnson, DJ Orton, A Apffel, YM Ibrahim, ME Monroe, RJ Moore, JN Smith, J Ma, RS Renslow, DG Thomas, AE Blackwell, G  Swinford, J Sausen, RT Kurulugama, N Eno, E Darland, G Stafford, J Fjeldsted, TO Metz, JG Teeguarden, RD Smitha, ES Baker (2016) SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids 2016 Dec. Clinical Mass Spectrometry
  3. Takamiya M, Sakurai M, Teranishi F, Ikeda T, Kamiyama T, Asai A. (2016) Lead discovery for mammalian elongation of long chain fatty acids family 6 using a combination of high-throughput fluorescent-based assay and RapidFire mass spectrometry assay. Biochemical and Biophysical Research Communications. 2016 Oct 25. pii: S0006-291X(16)31789-2. Epub ahead of print
  4. Mesleh MF, Rajaratnam P, Conrad M, Chandrasekaran V, Liu CM, Pandya BA, Hwang YS, Rye PT, Muldoon C, Becker B, Zuegg J, Meutermans W, Moy TI. (2016) Targeting Bacterial Cell Wall Peptidoglycan Synthesis by Inhibition of Glycosyltransferase Activity. Chemical Biology & Drug Design. 2016 Feb;87(2):190-9. doi: 10.1111/cbdd.12662. Epub 2015 Oct 9.
  5. Dovala D, Rath CM, Hu Q, Sawyer WS, Shia S, Elling RA, Knapp MS, Metzger LE 4th. (2016) Structure-guided enzymology of the lipid A acyltransferase LpxM reveals a dual activity mechanism. Proceedings of the National Academy of Sciences, USA (PNAS). 2016 Oct 11;113(41):E6064-E6071. Epub 2016 Sep 28.
  6. Vrobel I, Janečková H, Faber E, Bouchalová K, Mičová K, Friedecký D, Adam T. (2016) Ultrafast Online SPE-MS/MS Method for Quantification of 3 Tyrosine Kinase Inhibitors in Human Plasma. Therapeutic Drug Monitoring. 2016 Aug;38(4):516-24.
  7. Wagner AD, Elkin L, Mosure K, Gallagher L, Stavola LK, Soars MG, Shou W. (2016) Development of a high-throughput mass spectrometry based analytical method to support an in vitro OATP1B1 inhibition screening assay. Rapid Communications in Mass Spectronomy. 2016 Aug 15;30(15):1787-96.
  8. Rohman M, Wingfield J. (2016) High-Throughput Screening Using Mass Spectrometry within Drug Discovery. Methods Molecular Biol. 2016;1439:47-63.
  9. Langman LJ, Danso D, Robert E, Jannetto PJ. (2016) High-Throughput Quantitation of Busulfan in Plasma Using Ultrafast Solid-Phase Extraction Tandem Mass Spectrometry (SPE-MS/MS). Methods Molecular Biol. 2016;1383:89-95
  10. Neifeld JR, Regester LE, Holler JM, Vorce SP, Magluilo J Jr, Ramos G, Bosy TZ. (2016) Ultrafast Screening of Synthetic Cannabinoids and Synthetic Cathinones in Urine by RapidFire-Tandem Mass Spectrometry. J Anal Toxicology. 2016 Jun;40(5):379-87.
  11. Jannetto PJ, Langman LJ. (2016) High-throughput online solid-phase extraction tandem mass spectrometry: Is it right for your clinical laboratory? Clinical Biochem. 2016 Apr 27. pii: S0009-9120(16)30043-1. [Epub ahead of print]
  12. Amaral A, Saran C, Amin J, Hatsis P.A. (2016) Comparison of LC-MS/MS and a Fully Integrated Autosampler/Solid-Phase Extraction System for the Analysis of Protein Binding Samples. J Biomolecular Screening. 2016 Jul;21(6):620-5. Epub 2016 Feb 22.
  13. Lu H, Kopcho L, Ghosh K, Witmer M, Parker M, Gupta S, Paul M, Krishnamurthy P, Laksmaiah B, Xie D, Tredup J, Zhang L, Abell LM. (2016) Development of a RapidFire mass spectrometry assay and a fluorescence assay for the discovery of kynurenine aminotransferase II inhibitors to treat central nervous system disorders. Anal Biochemistry. 2016 May 15;501:56-65.Epub 2016 Feb 11.
  14. Campuzano ID, San Miguel T, Rowe T, Onea D, Cee VJ, Arvedson T, McCarter JD. (2016) High-Throughput Mass Spectrometric Analysis of Covalent Protein-Inhibitor Adducts for the Discovery of Irreversible Inhibitors: A Complete Workflow. J Biomol Screening. 2016 Feb;21(2):136-44. Epub 2015 Dec 16.
  15. Leveridge M, Collier L, Edge C, Hardwicke P, Leavens B, Ratcliffe S, Rees M, Stasi LP, Nadin A, Reith AD. (2016) A High-Throughput Screen to Identify LRRK2 Kinase Inhibitors for the Treatment of Parkinson’s Disease Using RapidFire Mass Spectrometry. J Biomol Screening. 2016 Feb;21(2):145-55. Epub 2015 Sep 24.
  16. Gordon LJ, Allen M, Artursson P, Hann MM, Leavens BJ, Mateus A, Readshaw S, Valko K, Wayne GJ, West A. (2016) Direct Measurement of Intracellular Compound Concentration by RapidFire Mass Spectrometry Offers Insights into Cell Permeability. J Biomol Screen. 2016 Feb;21(2):156-64. Epub 2015 Sep 3.
  17. Maegley KA, Krivacic C, Bingham P, Liu W, Brooun A. Comparison of a High-Throughput Mass Spectrometry Method and Radioactive Filter Binding to Assay the Protein Methyltransferase PRMT5. Assay and Drug Development Technology. 2015 May;13(4):235-40.
  18. Danso D, Jannetto PJ, Enger R, Langman LJ (2015) High-Throughput Validated Method for the Quantitation of Busulfan in Plasma Using Ultrafast SPE-MS/MS, Therapeutic Drug Monitoring, 37(3): 319-24
  19. Rye PT, LaMarr WA (2015) Measurement of Glycolysis Reactants by High-Throughput Solid Phase Extraction with tandem Mass Spectrometry: Characterization of Pyrophosphate-dependent phosphofructokinase as a case Study, Analytical Biochemistry, 482: 40-7
  20. Sato K, Takahagi H, Yoshikawa T, Morimoto S, Takai T, Hidaka K, Kamaura M, Kubo O, Adachi R, Ishii T, Maki T, Mochida T, Takekawa S, Nakakariya M, Amano N, Kitazaki T. (2015) Discovery of a Novel Series of N-Phenylindoline-5-sulfonamide Derivatives as Potent, Selective, and Orally Bioavailable Acyl CoA: Monoacylglycerol Acyltransferase-2 Inhibitors. Journal Medicinal Chem. 2015 May 14;58(9):3892-909.Epub 2015 Apr 30.
  21. Meng J, Lai MT, Munshi V, Grobler J, McCauley J, Zuck P, Johnson EN, Uebele VN, Hermes JD, Adam GC (2015) Screening of HIV-1 Protease Using a Combination of an Ultra-High-Throughput Fluorescent-Based Assay and RapidFire Mass Spectrometry, Journal of Biomolecular Screening, 20(5): 606-15
  22. Adam GC, Meng J, Rizzo JM, Amoss A, Lusen JW, Patel A, Riley D, Hunt R, Zuck P, Johnson EN, Uebele VN, Hermes JD (2015) Use of High-Throughput Mass Spectrometry to Reduce False Positives in Protease uHTS Screens, Journal of Biomolecular Screening, 20(2): 212-22
  23. Grote-Koska D, Czajkowski S, Brand K (2015) Performance of the new RapidFire system for therapeutic monitoring of immunosuppressants. Therapeutic Drug Monitoring, 37(3): 400-4
  24. Korman E, Langman LJ, Jannetto PJ (2015) High-Throughput Method for the Quantification of Lacosamide in Serum using Ultra-Fast SPE-MS/MS, Therapeutic Drug Monitoring, 37(1): 126-31
  25. Shimada T, Kelly J, LaMarr WA, van Vlies N, Yasuda E, Mason RW, Mackenzie W, Kubaski F, Giugliani R, Chinen Y, Yamaguchi S, Suzuki Y, Orii KE, Fukao T, Orii T, Tomatsu S (2014) Novel heparan sulfate assay by using automated high-throughput mass spectrometry: Application to monitoring and screening for mucopolysaccharidoses, Molecular Genetics and Metabolism, 113(1-2): 92-9
  26. Tomatsu S, Shimada T, Mason RW, Montaño AM, Kelly J, LaMarr WA, Kubaski F, Giugliani R, Guha A, Yasuda E, Mackenzie W, Yamaguchi S, Suzuki Y, Orii T (2014) Establishment of glycosaminoglycan assays for mucopolysaccharidoses, Metabolites, 4(3): 655-79
  27. Brooks E, Wu X, Hanel A, Nguyen S, Wang J, Zhang JH, Harrison A, Zhang W (2014) Identification and Characterization of Small-Molecule Inhibitors of the R132H/R132H Mutant Isocitrate Dehydrogenase 1 Homodimer and R132H/Wild-Type Heterodimer, Journal of Biomolecular Screening, 19(8): 1193-1200
  28. Li AP, Schlicht KE (2014) Application of a higher throughput approach to derive apparent michaelis-menten constants of isoform-selective p450-mediated biotransformation reactions in human hepatocytes, Drug Metabolism Letters, 8(1): 2-11
  29. Lowe DM, Gee M, Haslam C, Leavens B, Christodoulou E, Hissey P, Hardwicke P, Argyrou A, Webster SP, Mole DJ, Wilson K, Binnie M, Yard BA, Dean T, Liddle J, Uings I, Hutchinson JP (2014) Lead discovery for human kynurenine 3-monooxygenase by high-throughput RapidFire mass spectrometry, Journal of Biomolecular Screening, 19(4): 508-15
  30. Tomatsu S, Shimada T, Mason RW, Kelly J, LaMarr WA, Yasuda E, Shibata Y, Futatsumori H, Montaño AM, Yamaguchi S, Suzuki Y, Orii T (2014) Assay for Glycosaminoglycans by Tandem Mass Spectrometry and its Applications, Journal of Analytical & Bioanalytical Techniques, Suppl 2: 6
  31. Leveridge M, Buxton R, Argyrou A, Francis P, Leavens B, West A, Rees M, Hardwicke P, Bridges A, Ratcliffe S, Chung CW (2014) Demonstrating enhanced throughput of RapidFire mass spectrometry through multiplexing using the JmjD2d demethylase as a model system, Journal of Biomolecular Screening, 19(2): 278-86
  32. Vanderporten E, Frick L, Turincio R, Thana P, Lamarr W, Liu Y (2013) Label-free high-throughput assays to screen and characterize novel lactate dehydrogenase inhibitors, Analytical Biochemistry, 441(2): 115-22
  33. Rendina AR, Pietrak B, Smallwood A, Zhao H, Qi H, Quinn C, Adams ND, Concha N, Duraiswami C, Thrall SH, Sweitzer S, Schwartz B. (2013) Mutant IDH1 enhances the production of 2-hydroxyglutarate due to its kinetic mechanism. Biochemistry. 2013 Jul 2;52(26):4563-77. Epub 2013 Jun 21.
  34. Miller VP, SPE-MS analysis of absorption, distribution, metabolism and excretion assays: a tool to increase throughput and steamline workflow. Bioanalysis. 2012 May;4(9):1111-21.
  35. Razavi M, Frick LE, LaMarr WA, Pope ME, Miller CA, Anderson NL, Pearson TW (2012) High-throughput SISCAPA quantitation of peptides from human plasma digests by ultrafast, liquid chromatography-free mass spectrometry, Journal of Proteome Research, 11(12): 5642-9
  36. Wu X, Wang J, Tan L, Bui J, Gjerstad E, McMillan K, Zhang W (2012) In vitro ADME profiling using high-throughput rapidfire mass spectrometry: cytochrome p450 inhibition and metabolic stability assays, Journal of Biomolecular Screening, 17(6): 761-72
  37. Leveridge MV, Bardera AI, LaMarr W, Billinton A, Bellenie B, Edge C, Francis P, Christodoulou E, Shillings A, Hibbs M, Fosberry A, Tanner R, Hardwicke P, Craggs P, Sinha Y, Elegbe O, Alvarez-Ruiz E, Martin-Plaza JJ, Barroso-Poveda V, Baddeley S, Chung CW, Hutchinson J (2012) Lead discovery for microsomal prostaglandin E synthase using a combination of high-throughput fluorescent-based assays and RapidFire mass spectrometry, Journal of Biomolecular Screening, 17(5): 641-50
  38. Hutchinson SE, Leveridge MV, Heathcote ML, Francis P, Williams L, Gee M, Munoz-Muriedas J, Leavens B, Shillings A, Jones E, Homes P, Baddeley S, Chung CW, Bridges A, Argyrou A (2012) Enabling lead discovery for histone lysine demethylases by high-throughput RapidFire mass spectrometry, Journal of Biomolecular Screening, 17(1): 39-48
  39. Holt, Wang, Chen, Choi, Geoghagen, Jensen, Jonas, Luo, LaMarr, Malkowitz, Ozbal, Xiong, Dufresne, Luo. (2011) Expanding the Scope of HTMS Methods, Label-Free Technologies For Drug Discovery. Publisher: John Wiley & Sons, Inc
  40. Rye PT, Frick LE, Ozbal CC, Lamarr WA (2011) Advances in label-free screening approaches for studying sirtuin-mediated deacetylation, Journal of Biomolecular Screening, 16(10): 1217-26
  41. Rye PT, Frick LE, Ozbal CC, Lamarr WA (2011) Advances in label-free screening approaches for studying histone acetyltransferases (HATs), Journal of Biomolecular Screening, 16(10): 1186-95
  42. Luippold AH1, Arnhold T, Jörg W, Krüger B, Süssmuth RD. Application of a rapid and integrated analysis system (RIAS) as a high-throughput processing tool for in vitro ADME samples by liquid chromatography/tandem mass spectrometry. J Biomol Screen. 2011 Mar;16(3):370-7. Epub 2011 Feb 18.
  43. Luippold AH1, Arnhold T, Jörg W, Krüger B, Süssmuth RD. An integrated platform for fully automated high-throughput LC–MS/MS analysis of in vitro metabolic stability assay samples. International Journal of Mass Spectrometry, epub 17 July 2010
  44. Plant M, Dineen T, Cheng A, Long AM, Chen H, Morgenstern KA (2011) Screening for lysine-specific demethylase-1 inhibitors using a label-free high-throughput mass spectrometry assay, Analytical Biochemistry, 419(2): 217-27
  45. Jian W, Romm MV, Edom RW, Miller VP, LaMarr WA, Weng N (2011) Evaluation of a high-throughput online solid phase extraction-tandem mass spectrometry system for in vivo bioanalytical studies, Analytical Chemistry, 83(21): 8259-66
  46. Wagner AD, Kolb JM, Ozbal CC, Herbst JJ, Olah TV, Weller HN, Zvyaga TA, Shou WZ (2011) Ultrafast mass spectrometry based bioanalytical method for digoxin supporting an in vitro P-glycoprotein (P-gp) inhibition screen, Rapid Communications in Mass Spectrometry, 25(9): 1231-40
  47. Atkinson KA, Beretta EE, Brown JA, Castrodad M, Chen Y, Cosgrove JM, Du P, Litchfield J, Makowski M, Martin K, McLellan TJ, Neagu C, Perry DA, Piotrowski DW, Steppan CM, Trilles R (2011) N-benzylimidazole carboxamides as potent orally active stearoylCoA desaturase-1 inhibitors, Bioorganic & Medicinal Chemistry Letters, 21(6): 1621-5
  48. Highkin MK, Yates MP, Nemirovskiy OV, Lamarr WA, Munie GE, Rains JW, Masferrer JL, Nagiec MM (2011) High-throughput screening assay for sphingosine kinase inhibitors in whole blood using RapidFire® mass spectrometry, Journal of Biomolecular Screening, 16(2): 272-7
  49. Brown A, Bickford S, Hatsis P, Amin J, Bell L, Harriman S. (2010) High-throughput analysis of in vitro cytochrome p450 inhibition samples using mass spectrometry coupled with an integrated liquid chromatography/autosampler system. Rapid Commununications in Mass Spectronomy. 2010 Apr 30;24(8):1207-10.
  50. Lim KB, Ozbal CC, Kassel DB (2010) Development of a high-throughput online solid-phase extraction/tandem mass spectrometry method for cytochrome P450 inhibition screening, Journal of Biomolecular Screening, 15(4): 447-52
  51. Langsdorf EF, Malikzay A, Lamarr WA, Daubaras D, Kravec C, Zhang R, Hart R, Monsma F, Black T, Ozbal CC, Miesel L, Lunn CA (2010) Screening for antibacterial inhibitors of the UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) using a high-throughput mass spectrometry assay, Journal of Biomolecular Screening, 15(1): 52-61
  52. Holt TG, Choi BK, Geoghagen NS, Jensen KK, Luo Q, LaMarr WA, Makara GM, Malkowitz L, Ozbal CC, Xiong Y, Dufresne C, Luo MJ (2009) Label-free high-throughput screening via mass spectrometry: a single cystathionine quantitative method for multiple applications, Assay and Drug Development Technologies, 7(5): 495-506
  53. Jonas M, LaMarr WA, Ozbal C (2009) Mass spectrometry in high-throughput screening: a case study on acetyl-coenzyme a carboxylase using RapidFire–mass spectrometry (RF-MS), Combinatorial Chemistry & High Throughput Screening, 12(8): 752-9
  54. Soulard P, McLaughlin M, Stevens J, Connolly B, Coli R, Wang L, Moore J, Kuo MS, LaMarr WA, Ozbal CC, Bhat BG (2008) Development of a high-throughput screening assay for stearoyl-CoA desaturase using rat liver microsomes, deuterium labeled stearoyl-CoA and mass spectrometry, Analytica Chimica Acta, 627(1): 105-11
  55. Shiau AK, Massari ME, Ozbal CC (2008) Back to basics: label-free technologies for small molecule screening, Combinatorial Chemistry & High Throughput Screening, 11(3): 231-7
  56. Quercia AK, LaMarr WA, Myung J, Ozbal CC, Landro JA, Lumb KJ (2007) High-throughput screening by mass spectrometry: comparison with the scintillation proximity assay with a focused-file screen of AKT1/PKB alpha, Journal of Biomolecular Screening, 12(4): 473-80
  57. Forbes CD, Toth JG, Ozbal CC, Lamarr WA, Pendleton JA, Rocks S, Gedrich RW, Osterman DG, Landro JA, Lumb KJ (2007) High-throughput mass spectrometry screening for inhibitors of phosphatidylserine decarboxylase, Journal of Biomolecular Screening, 12(5): 628-34
  58. Ozbal CC, LaMarr WA, Linton JR, Green DF, Katz A, Morrison TB, Brenan CJ (2004) High throughput screening via mass spectrometry: a case study using acetylcholinesterase, Assay and Drug Development Technologies, 2(4): 373-81