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Purkey, Hans
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Purkey, Hans

Graduate Student
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Positions

  • 2016 - Senior Scientist, Genentech

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  • Doctoral Dissertation
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Publications

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  • academic article

    • Bronner, S. M., Merrick, K. A., Murray, J., Salphati, L., Moffat, J. G., Pang, J., Sneeringer, C. J., Dompe, N., Cyr, P., Purkey, H., Boenig, G. D., Li, J., et al. Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma Bioorganic & Medicinal Chemistry Letters  2019 29:2294-2301  DOI:10.1016/j.bmcl.2019.06.021  PMID:31307887
    • Ladi, E., Everett, C., Stivala, C. E., Daniels, B. E., Durk, M. R., Harris, S. F., Huestis, M. P., Purkey, H. E., Staben, S. T., Augustin, M., Blaesse, M., Steinbacher, S., et al. Design and evaluation of highly selective human immunoproteasome inhibitors reveal a compensatory process that preserves immune cell viability Journal of Medicinal Chemistry  2019 62:7032-7041  DOI:10.1021/acs.jmedchem.9b00509  PMID:31283222
    • Alexander, M. K., Miu, A., Oh, A., Reichelt, M., Ho, H., Chalouni, C., Labadie, S., Wang, L., Liang, J., Nickerson, N. N., Hu, H., Yu, L., et al. Disrupting gram-negative bacterial outer membrane biosynthesis through inhibition of the lipopolysaccharide transporter MsbA Antimicrobial Agents and Chemotherapy  2018 62:e01142-18  DOI:10.1128/aac.01142-18  PMID:30104274  PMCID:PMC6201111
    • Ho, H., Miu, A., Alexander, M. K., Garcia, N. K., Oh, A., Zilberleyb, I., Reichelt, M., Austin, C. D., Tam, C., Shriver, S., Hu, H., Labadie, S. S., et al. Structural basis for dual-mode inhibition of the ABC transporter MsbA Nature  2018 557:196-201  DOI:10.1038/s41586-018-0083-5  PMID:29720648
    • Chan, B. K., Hanan, E. J., Bowman, K. K., Bryan, M. C., Burdick, D., Chan, E., Chen, Y., Clausen, S., Dela Vega, T., Dotson, J., Eigenbrot, C., Elliott, R. L., et al. Discovery of a noncovalent, mutant-selective epidermal growth factor receptor inhibitor Journal of Medicinal Chemistry  2016 59:9080-9093  DOI:10.1021/acs.jmedchem.6b00995  PMID:27564586
    • Purkey, H. E., Robarge, K., Chen, J., Chen, Z., Corson, L. B., Ding, C. Z., DiPasquale, A. G., Dragovich, P. S., Eigenbrot, C., Evangelista, M., Fauber, B. P., Gao, Z., et al. Cell active hydroxylactam inhibitors of human lactate dehydrogenase with oral bioavailability in mice ACS Medicinal Chemistry Letters  2016 7:896-901  DOI:10.1021/acsmedchemlett.6b00190  PMID:27774125  PMCID:PMC5066143
    • Boudreau, A., Purkey, H. E., Hitz, A., Robarge, K., Peterson, D., Labadie, S., Kwong, M., Hong, R., Gao, M., Del Nagro, C., Pusapati, R., Ma, S., et al. Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition Nature Chemical Biology  2016 12:779-786  DOI:10.1038/nchembio.2143  PMID:27479743
    • Hanan, E. J., Baumgardner, M., Bryan, M. C., Chen, Y., Eigenbrot, C., Fan, P., Gu, X. H., La, H., Malek, S., Purkey, H. E., Schaefer, G., Schmidt, S., et al. 4-Aminoindazolyl-dihydrofuro 3,4-d pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase Bioorganic & Medicinal Chemistry Letters  2016 26:534-539  DOI:10.1016/j.bmcl.2015.11.078  PMID:26639762
    • Bryan, M. C., Burdick, D. J., Chan, B. K., Chen, Y., Clausen, S., Dotson, J., Eigenbrot, C., Elliott, R., Hanan, E. J., Heald, R., Jackson, P., La, H., et al. Pyridones as highly selective, noncovalent inhibitors of T790M double mutants of EGFR ACS Medicinal Chemistry Letters  2016 7:100-104  DOI:10.1021/acsmedchemlett.5b00428  PMID:26819674  PMCID:PMC4716594
    • Heald, R., Bowman, K. K., Bryan, M. C., Burdick, D., Chan, B., Chan, E., Chen, Y., Clausen, S., Dominguez-Fernandez, B., Eigenbrot, C., Elliott, R., Hanan, E. J., et al. Noncovalent mutant selective epidermal growth factor receptor inhibitors: a lead optimization case study Journal of Medicinal Chemistry  2015 58:8877-8895  DOI:10.1021/acs.jmedchem.5b01412
    • Labadie, S., Dragovich, P. S., Chen, J., Fauber, B. P., Boggs, J., Corson, L. B., Ding, C. Z., Eigenbrot, C., Ge, H., Ho, Q., Lai, K. W., Ma, S., et al. Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase Bioorganic & Medicinal Chemistry Letters  2015 25:75-82  DOI:10.1016/j.bmcl.2014.11.008  PMID:25466195
    • Fauber, B. P., Dragovich, P. S., Chen, J., Corson, L. B., Ding, C. Z., Eigenbrot, C., Labadie, S., Malek, S., Peterson, D., Purkey, H. E., Robarge, K., Sideris, S., et al. Identification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase Bioorganic & Medicinal Chemistry Letters  2014 24:5683-5687  DOI:10.1016/j.bmcl.2014.10.067  PMID:25467161
    • Thomas, A. A., Hunt, K. W., Newhouse, B., Watts, R. J., Liu, X., Vigers, G., Smith, D., Rhodes, S. P., Brown, K. D., Otten, J. N., Burkard, M., Cox, A. A., et al. 8-Tetrahydropyran-2-yl chromans: highly selective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors Journal of Medicinal Chemistry  2014 57:10112-10129  DOI:10.1021/jm5015132  PMID:25411915
    • Hanan, E. J., Eigenbrot, C., Bryan, M. C., Burdick, D. J., Chan, B. K., Chen, Y., Dotson, J., Heald, R. A., Jackson, P. S., La, H., Lainchbury, M. D., Malek, S., et al. Discovery of selective and noncovalent diaminopyrimidine-based inhibitors of epidermal growth factor receptor containing the T790M resistance mutation Journal of Medicinal Chemistry  2014 57:10176-10191  DOI:10.1021/jm501578n  PMID:25383627  PMCID:PMC4266342
    • Tao, Z. F., Hasvold, L., Wang, L., Wang, X., Petros, A. M., Park, C. H., Boghaert, E. R., Catron, N. D., Chen, J., Colman, P. M., Czabotar, P. E., Deshayes, K., et al. Discovery of a potent and selective BCL-X-L inhibitor with in vivo activity ACS Medicinal Chemistry Letters  2014 5:1088-1093  DOI:10.1021/ml5001867  PMID:25313317
    • Dragovich, P. S., Fauber, B. P., Boggs, J., Chen, J., Corson, L. B., Ding, C. Z., Eigenbrot, C., Ge, H., Giannetti, A. M., Hunsaker, T., Labadie, S., Li, C., et al. Identification of substituted 3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase Bioorganic & Medicinal Chemistry Letters  2014 24:3764-3771  DOI:10.1016/j.bmcl.2014.06.076  PMID:25037916
    • Volgraf, M., Chan, L., Huestis, M. P., Purkey, H. E., Burkard, M., Do, M. G., Harris, J., Hunt, K. W., Liu, X., Lyssikatos, J. P., Rana, S., Thomas, A. A., et al. Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors Bioorganic & Medicinal Chemistry Letters  2014 24:2477-2480  DOI:10.1016/j.bmcl.2014.04.012  PMID:24780121
    • Thomas, A. A., Hunt, K. W., Volgraf, M., Watts, R. J., Liu, X., Vigers, G., Smith, D., Sammond, D., Tang, T. P., Rhodes, S. P., Metcalf, A. T., Brown, K. D., et al. Discovery of 7-tetrahydropyran-2-yl chromans: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors that reduce amyloid β-protein (Aβ) in the central nervous system Journal of Medicinal Chemistry  2014 57:878-902  DOI:10.1021/jm401635n  PMID:24397738
    • Huestis, M. P., Liu, W., Volgraf, M., Purkey, H. E., Yu, C., Wang, W. R., Smith, D., Vigers, G., Dutcher, D., Hunt, K. W., Siu, M. Diethylaminosulfur trifluoride-mediated intramolecular cyclization of 2-hydroxycycloalkylureas to fused bicyclic aminooxazoline compounds and evaluation of their biochemical activity against beta-secretase-1 (BACE-1) Tetrahedron Letters  2013 54:5802-5807  DOI:10.1016/j.tetlet.2013.07.136
    • Dragovich, P. S., Fauber, B. P., Corson, L. B., Ding, C. Z., Eigenbrot, C., Ge, H., Giannetti, A. M., Hunsaker, T., Labadie, S., Liu, Y., Malek, S., Pan, B., et al. Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase Bioorganic & Medicinal Chemistry Letters  2013 23:3186-3194  DOI:10.1016/j.bmcl.2013.04.001  PMID:23628333
    • Hunt, K. W., Cook, A. W., Watts, R. J., Clark, C. T., Vigers, G., Smith, D., Metcalf, A. T., Gunawardana, I. W., Burkard, M., Cox, A. A., Do, M. K. G., Dutcher, D., et al. Spirocyclic β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: from hit to lowering of cerebrospinal fluid (CSF) amyloid β in a higher species Journal of Medicinal Chemistry  2013 56:3379-3403  DOI:10.1021/jm4002154  PMID:23537249
    • Long, D. D., Frieman, B., Hegde, S. S., Hill, C. M., Jiang, L., Kintz, S., Marquess, D. G., Purkey, H., Shaw, J. P., Steinfeld, T., Wilson, M. S., Wrench, K. A multivalent approach towards linked dual-pharmacology prostaglandin F receptor agonist/carbonic anhydrase-II inhibitors for the treatment of glaucoma Bioorganic & Medicinal Chemistry Letters  2013 23:939-943  DOI:10.1016/j.bmcl.2012.12.058  PMID:23317571
    • Ameriks, M. K., Bembenek, S. D., Burdett, M. T., Choong, I. C., Edwards, J. P., Gebauer, D., Gu, Y., Karlsson, L., Purkey, H. E., Staker, B. L., Sun, S., Thurmond, R. L., et al. Diazinones as P2 replacements for pyrazole-based cathepsin S inhibitors Bioorganic & Medicinal Chemistry Letters  2010 20:4060-4064  DOI:10.1016/j.bmcl.2010.05.086  PMID:20541404
    • Fucini, R. V., Hanan, E. J., Romanowski, M. J., Elling, R. A., Lew, W., Barr, K. J., Zhu, J., Yoburn, J. C., Liu, Y., Fahr, B. T., Fan, J., Lu, Y., et al. Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors Bioorganic & Medicinal Chemistry Letters  2008 18:5648-5652  DOI:10.1016/j.bmcl.2008.08.095  PMID:18793847
    • Hanan, E. J., Fucini, R. V., Romanowski, M. J., Elling, R. A., Lew, W., Purkey, H. E., VanderPorten, E. C., Yang, W. Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors Bioorganic & Medicinal Chemistry Letters  2008 18:5186-5189  DOI:10.1016/j.bmcl.2008.08.091  PMID:18790636
    • Fahr, B. T., O'Brien, T., Pham, P., Waal, N. D., Baskaran, S., Raimundo, B. C., Lam, J. W., Sopko, M. M., Purkey, H. E., Romanowski, M. J. Tethering identifies fragment that yields potent inhibitors of human caspase-1 Bioorganic & Medicinal Chemistry Letters  2006 16:559-562  DOI:10.1016/j.bmcl.2005.10.048  PMID:16274992
    • degree-related publication Petrassi, H. M., Johnson, S. M., Purkey, H. E., Chiang, K. P., Walkup, T., Jiang, X., Powers, E. T., Kelly, J. W. Potent and selective structure-based dibenzofuran inhibitors of transthyretin amyloidogenesis: Kinetic stabilization of the native state Journal of the American Chemical Society  2005 127:6662-6671  DOI:10.1021/ja044351f  PMID:15869287
    • O'Brien, T., Fahr, B. T., Sopko, M. M., Lam, J. W., Waal, N. D., Raimundo, B. C., Purkey, H. E., Pham, P., Romanowski, M. J. Structural analysis of caspase-1 inhibitors derived from Tethering Acta Crystallographica Section F-Structural Biology and Crystallization Communications  2005 61:451-458  DOI:10.1107/s1744309105010109  PMID:16511067  PMCID:PMC1952309
    • degree-related publication Johnson, S. M., Petrassi, H. M., Palaninathan, S. K., Mohamedmohaideen, N. N., Purkey, H. E., Nichols, C., Chiang, K. P., Walkup, T., Sacchettini, J. C., Sharpless, K. B., Kelly, J. W. Bisaryloxime ethers as potent inhibitors of transthyretin amyloid fibril formation Journal of Medicinal Chemistry  2005 48:1576-1587  DOI:10.1021/jm049274d  PMID:15743199
    • degree-related publication Razavi, H., Powers, E. T., Purkey, H. E., Adamski-Werner, S. L., Chiang, K. P., Dendle, M. T. A., Kelly, J. W. Design, synthesis, and evaluation of oxazole transthyretin amyloidogenesis inhibitors Bioorganic & Medicinal Chemistry Letters  2005 15:1075-1078  DOI:10.1016/j.bmcl.2004.12.022  PMID:15686915
    • degree-related publication Purkey, H. E., Palaninathan, S. K., Kent, K. C., Smith, C., Safe, S. H., Sacchettini, J. C., Kelly, J. W. Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity Chemistry & Biology  2004 11:1719-1728  DOI:10.1016/j.chembiol.2004.10.009  PMID:15610856
    • degree-related publication Razavi, H., Palaninathan, S. K., Powers, E. T., Wiseman, R. L., Purkey, H. E., Mohamedmohaideen, N. N., Deechongkit, S., Chiang, K. P., Dendle, M. T. A., Sacchettini, J. C., Kelly, J. W. Benzoxazoles as transthyretin amyloid fibril inhibitors: Synthesis, evaluation, and mechanism of action Angewandte Chemie-International Edition  2003 42:2758-2761  DOI:10.1002/anie.200351179  PMID:12820260
    • degree-related publication McCammon, M. G., Scott, D. J., Keetch, C. A., Greene, L. H., Purkey, H. E., Petrassi, H. M., Kelly, J. W., Robinson, C. V. Screening transthyretin amyloid fibril inhibitors: Characterization of novel multiprotein, multiligand complexes by mass spectrometry Structure  2002 10:851-863  DOI:10.1016/s0969-2126(02)00771-2  PMID:12057199
    • degree-related publication Purkey, H. E., Dorrell, M. I., Kelly, J. W. Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma Proceedings of the National Academy of Sciences of the United States of America  2001 98:5566-5571  DOI:10.1073/pnas.091431798  PMID:11344299  PMCID:PMC33253
    • degree-related publication Oza, V. B., Petrassi, H. M., Purkey, H. E., Kelly, J. W. Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors Bioorganic & Medicinal Chemistry Letters  1999 9:1-6  DOI:10.1016/s0960-894x(98)00696-9  PMID:9990446
    • degree-related publication Peterson, S. A., Klabunde, T., Lashuel, H. A., Purkey, H., Sacchettini, J. C., Kelly, J. W. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation Proceedings of the National Academy of Sciences of the United States of America  1998 95:12956-12960  DOI:10.1073/pnas.95.22.12956  PMID:9789022
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Background

education and training

  • Ph.D. in Biology, Scripps Research 1996 - 2002
  • B.S. in Chemistry, Harvey Mudd College 1992 - 1996

advisee of

  • graduate advising relationship

    • Kelly, Jeffery, Ph.D.  candidacy, 1997 - 2002
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Contact

full name

  • Hans Edward Purkey

geographic location

  • Scripps California 

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