Duckett, Derek

Faculty Member

Positions

2005 - Associate Scientific Director I, Translational Research Institute , Scripps Research
2017 - 2018 Associate Professor of Molecular Medicine, Molecular Medicine , Scripps Research
2005 - 2018 Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
2015 - 2017 Associate Professor of Molecular Therapeutics, Molecular Therapeutics , Scripps Research
2005 - 2015 Assistant Professor, Molecular Therapeutics , Scripps Research

Work in our laboratory is aimed at evaluating small molecule kinase inhibitors of biologic and therapeutic interest. We are currently involved in refining a novel class of kinase inhibitors aimed at the therapeutic treatment of human diseases such as Parkinson’s Disease and Cancer. Protein kinases are important components of signal transduction pathways and deregulation of kinase activity can lead to human disease. Kinases have therefore become one of the most important target classes for drug development. Working closely with other disciplines such as chemistry, pharmacology, and drug metabolism, we aim to optimize lead compounds for potency and selectivity while minimizing toxicity to generate candidate molecules with appropriate drug like properties suitable for IND enabling and first time in human studies.

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recent publications

academic article
- Quereda, V., Bayle, S., Vena, F., Frydman, S. M., Monastyrskyi, A., Roush, W. R., Duckett, D. R. Therapeutic targeting of CDK12/CDK13 in triple-negative breast cancer Cancer Cell 2019 36:545-558 DOI:10.1016/j.ccell.2019.09.004 PMID:31668947
- Crawley, O., Opperman, K. J., Desbois, M., Adrados, I., Borgen, M. A., Giles, A. C., Duckett, D. R., Grill, B. Autophagy is inhibited by ubiquitin ligase activity in the nervous system Nature Communications 2019 10 DOI:10.1038/s41467-019-12804-3 PMID:31676756 PMCID:PMC6825199
- Quereda, V., Hou, S., Madoux, F., Scampavia, L., Spicer, T. P., Duckett, D. A cytotoxic three-dimensional-spheroid, high-throughput assay using patient-derived glioma stem cells SLAS Discovery 2018 23:842-849 DOI:10.1177/2472555218775055 PMID:29750582 PMCID:PMC6102052
- Monastyrskyi, A., Nilchan, N., Quereda, V., Noguchi, Y., Ruiz, C., Grant, W., Cameron, M., Duckett, D., Roush, W. Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer Bioorganic & Medicinal Chemistry 2018 26:590-602 DOI:10.1016/j.bmc.2017.12.020 PMID:29289448 PMCID:PMC5803353
- Monastyrskyi, A., Bayle, S., Quereda, V., Grant, W., Cameron, M., Duckett, D., Roush, W. Discovery of 2-arylquinazoline derivatives as a new class of ASK1 inhibitors Bioorganic & Medicinal Chemistry Letters 2018 28:400-404 DOI:10.1016/j.bmcl.2017.12.026 PMID:29277458
- Wood, S. D., Grant, W., Adrados, I., Choi, J. Y., Alburger, J. M., Duckett, D. R., Roush, W. R. In silica HTS and structure based optimization of indazole-derived ULK1 inhibitors ACS Medicinal Chemistry Letters 2017 8:1258-1263 DOI:10.1021/acsmedchemlett.7b00344 PMID:29259744 PMCID:PMC5733266
- Velagapudi, S. P., Cameron, M. D., Haga, C. L., Rosenberg, L. H., Lafitte, M., Duckett, D. R., Phinney, D. G., Disney, M. D. Design of a small molecule against an oncogenic noncoding RNA Proceedings of the National Academy of Sciences of the United States of America 2016 113:5898-5903 DOI:10.1073/pnas.1523975113 PMID:27170187 PMCID:PMC4889373
- Rosenberg, L. H., Lafitte, M., Quereda, V., Grant, W., Chen, W., Bibian, M., Noguchi, Y., Fallahi, M., Yang, C., Chang, J. C., Roush, W. R., Cleveland, J. L., et al. Therapeutic targeting of casein kinase 1δ in breast cancer Science Translational Medicine 2015 7:318ra202 DOI:10.1126/scitranslmed.aac8773 PMID:26676609 PMCID:PMC4809734
- Saunders, V. C., Lafitte, M., Adrados, I., Quereda, V., Feurstein, D., Ling, Y., Fallahi, M., Rosenberg, L. H., Duckett, D. R. Identification of an EGFRvIII-JNK2-HGF/c-Met-signaling axis required for intercellular crosstalk and glioblastoma multiforme cell invasion Molecular Pharmacology 2015 88:962-969 DOI:10.1124/mol.115.097774 PMID:26452771
- Rosenberg, L. H., Lafitte, M., Grant, W., Chen, W., Cleveland, J. L., Duckett, D. R. Development of an HTS-compatible assay for the discovery of Ulk1 inhibitors Journal of Biomolecular Screening 2015 20:913-920 DOI:10.1177/1087057115579391 PMID:25851035 PMCID:PMC4744088
- Corzo, C. A., Mari, Y., Chang, M. R., Khan, T., Kuruvilla, D., Nuhant, P., Kumar, N., West, G. M., Duckett, D. R., Roush, W. R., Griffin, P. R. Antiproliferation activity of a small molecule repressor of liver receptor homolog 1 Molecular Pharmacology 2015 87:296-304 DOI:10.1124/mol.114.095554 PMID:25473120 PMCID:PMC4293447
- Sturchler, E., Chen, W., Spicer, T., Hodder, P., McDonald, P., Duckett, D. Development of an HTS-compatible assay for the discovery of ASK1 signalosome inhibitors using alphascreen technology Assay and Drug Development Technologies 2014 12:229-237 DOI:10.1089/adt.2013.558 PMID:24831789 PMCID:PMC4025566
- He, Y., Duckett, D., Chen, W., Ling, Y. Y., Cameron, M. D., Lin, L., Ruiz, C. H., Lograsso, P. V., Kamenecka, T. M., Koenig, M. Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors Bioorganic & Medicinal Chemistry Letters 2014 24:161-164 DOI:10.1016/j.bmcl.2013.11.052 PMID:24332487 PMCID:PMC4540177
- Bibian, M., Rahaim, R. J., Choi, J. Y., Noguchi, Y., Schurer, S., Chen, W. M., Nakanishi, S., Licht, K., Rosenberg, L. H., Li, L., Feng, Y., Cameron, M. D., et al. Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties Bioorganic & Medicinal Chemistry Letters 2013 23:4374-4380 DOI:10.1016/j.bmcl.2013.05.075 PMID:23787102 PMCID:PMC3783656
- Jiang, R., Frackowiak, B., Shin, Y. S., Song, X. Y., Chen, W. M., Lin, L., Cameron, M. D., Duckett, D. R., Kamenecka, T. M. Design and synthesis of 1-aryl-5-anilinoindazoles as c-Jun N-terminal kinase inhibitors Bioorganic & Medicinal Chemistry Letters 2013 23:2683-2687 DOI:10.1016/j.bmcl.2013.02.082 PMID:23518277
- Sturchler, E., Feurstein, D., Chen, W. M., McDonald, P., Duckett, D. Stress-induced nuclear import of apoptosis signal-regulating kinase 1 is mediated by karyopherin alpha 2/beta 1 heterodimer Biochimica et Biophysica Acta-Molecular Cell Research 2013 1833:583-592 DOI:10.1016/j.bbamcr.2012.10.023 PMID:23123190
- Song, X., He, Y., Koenig, M., Shin, Y., Noel, R., Chen, W., Ling, Y. Y., Feurstein, D., Lin, L., Ruiz, C. H., Cameron, M. D., Duckett, D. R., et al. Synthesis and SAR of 2,4-diaminopyrimidines as potent c-jun n-terminal kinase inhibitors MedChemComm 2012 3:238-243 DOI:10.1039/c1md00219h
- Song, X. Y., Chen, W. M., Lin, L., Ruiz, C. H., Cameron, M. D., Duckett, D. R., Kamenecka, T. M. Synthesis and SAR of 2-phenoxypyridines as novel c-Jun N-terminal kinase inhibitors Bioorganic & Medicinal Chemistry Letters 2011 21:7072-7075 DOI:10.1016/j.bmcl.2011.09.090 PMID:22004719
- Hara, M. R., Kovacs, J. J., Whalen, E. J., Rajagopal, S., Strachan, R. T., Grant, W., Towers, A. J., Williams, B., Lam, C. M., Xiao, K. H., Shenoy, S. K., Gregory, S. G., et al. A stress response pathway regulates DNA damage through beta(2)-adrenoreceptors and beta-arrestin-1 Nature 2011 477:349-353 DOI:10.1038/nature10368 PMID:21857681 PMCID:PMC3628753
- Noel, R., Shin, Y., Song, X. Y., He, Y. J., Koenig, M., Chen, W. M., Ling, Y. Y., Lin, L., Ruiz, C. H., LoGrasso, P., Cameron, M. D., Duckett, D. R., et al. Synthesis and SAR of 4-(pyrazol-3-yl)-pyridines as novel c-jun N-terminal kinase inhibitors Bioorganic & Medicinal Chemistry Letters 2011 21:2732-2735 DOI:10.1016/j.bmcl.2010.11.104 PMID:21185177 PMCID:PMC3081976
- Chambers, J. W., Pachori, A., Howard, S., Ganno, M., Hansen, D., Song, X. Y., Kamenecka, T., Duckett, D., Chen, W. M., Ling, Y. Y., Cherry, L., Cameron, M. D. Small molecule c-jun-N-terminal Kinase (JNK) inhibitors protect dopaminergic neurons in a model of Parkinson's Disease ACS Chemical Neuroscience 2011 2:198-206 DOI:10.1021/cn100109k PMID:21666839 PMCID:PMC3110074
- He, Y. J., Kamenecka, T. M., Shin, Y. S., Song, X. Y., Jiang, R., Noel, R., Duckett, D., Chen, W. M., Ling, Y. Y., Cameron, M. D., Lin, L., Khan, S., et al. Synthesis and SAR of novel quinazolines as potent and brain-penetrant c-jun N-terminal kinase (JNK) inhibitors Bioorganic & Medicinal Chemistry Letters 2011 21:1719-1723 DOI:10.1016/j.bmcl.2011.01.079 PMID:21316221 PMCID:PMC3052630
- Kumar, N., Kojetin, D. J., Solt, L. A., Kumar, K. G., Nuhant, P., Duckett, D. R., Cameron, M. D., Butler, A. A., Roush, W. R., Griffin, P. R., Burris, T. P. Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist ACS Chemical Biology 2011 6:218-222 DOI:10.1021/cb1002762 PMID:21090593 PMCID:PMC3076127
- Hahmann, C., Weiser, A., Duckett, D., Schroeter, T. A predictive nuclear translocation assay for spliced x-box-binding protein 1 identifies compounds with known organ toxicities Assay and Drug Development Technologies 2011 9:79-87 DOI:10.1089/adt.2010.0300 PMID:20858054
- Duckett, D. R., Cameron, M. D. Metabolism considerations for kinase inhibitors in cancer treatment Expert Opinion on Drug Metabolism & Toxicology 2010 6:1175-1193 DOI:10.1517/17425255.2010.506873 PMID:20684746 PMCID:PMC2940961
- Sturchler, E., Feurstein, D., McDonald, P., Duckett, D. Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation Biochemistry 2010 49:4094-4102 DOI:10.1021/bi100010j PMID:20364819
- Kamenecka, T., Jiang, R., Song, X. Y., Duckett, D., Chen, W. M., Ling, Y. Y., Habel, J., Laughlin, J. D., Chambers, J., Figuera-Losada, M., Cameron, M. D., Lin, L., et al. Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors Journal of Medicinal Chemistry 2010 53:419-431 DOI:10.1021/jm901351f PMID:19947601 PMCID:PMC2804074
- Yin, Y., Lin, L., Ruiz, C., Cameron, M. D., Pocas, J., Grant, W., Schroter, T., Chen, W. M., Duckett, D., Schurer, S., LoGrasso, P., Feng, Y. B. Benzothiazoles as Rho-associated kinase (ROCK-II) inhibitors Bioorganic & Medicinal Chemistry Letters 2009 19:6686-6690 DOI:10.1016/j.bmcl.2009.09.115 PMID:19837589
- Shin, Y. S., Chen, W. M., Habel, J., Duckett, D., Ling, Y. Y., Koenig, M., He, Y. J., Vojkovsky, T., LoGrasso, P., Kamenecka, T. M. Synthesis and sar of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors Bioorganic & Medicinal Chemistry Letters 2009 19:3344-3347 DOI:10.1016/j.bmcl.2009.03.086 PMID:19433357 PMCID:PMC2737472
- Kamenecka, T., Habel, J., Duckett, D., Chen, W. M., Ling, Y. Y., Frackowiak, B., Jiang, R., Shin, Y. S., Song, X. Y., LoGrasso, P. Structure-activity relationships and X-ray structures describing the selectivity of aminopyrazole inhibitors for c-jun N-terminal kinase 3 (JNK3) over p38 Journal of Biological Chemistry 2009 284:12853-12861 DOI:10.1074/jbc.M809430200 PMID:19261605 PMCID:PMC2676016
- Chen, Y. T., Bannister, T. D., Weiser, A., Griffin, E., Lin, L., Ruiz, C., Cameron, M. D., Schurer, S., Duckett, D., Schroter, T., LoGrasso, P., Feng, Y. B. Chroman-3-amides as potent Rho kinase inhibitors Bioorganic & Medicinal Chemistry Letters 2008 18:6406-6409 DOI:10.1016/j.bmcl.2008.10.080 PMID:18990570
- Heerding, D. A., Rhodes, N., Leber, J. D., Clark, T. J., Keenan, R. M., Lafrance, L. V., Li, M., Safonov, I. G., Takata, D. T., Venslavsky, J. W., Yamashita, D. S., Choudhry, A. E., et al. Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{ (3s)-3-piperidinylmethyl oxy}-1H-imidazo 4,5-c pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase Journal of Medicinal Chemistry 2008 51:5663-5679 DOI:10.1021/jm8004527 PMID:18800763
- Rhodes, N., Heerding, D. A., Duckett, D. R., Eberwein, D. J., Knick, V. B., Lansing, T. J., McConnell, R. T., Gilmer, T. M., Zhang, S. Y., Robell, K., Kahana, J. A., Geske, R. S., et al. Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity Cancer Research 2008 68:2366-2374 DOI:10.1158/0008-5472.can-07-5783 PMID:18381444
- Jiang, R., Duckett, D., Chen, W., Habel, J., Ling, Y. Y., LoGrasso, P., Kamenecka, T. M. 3,5-disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors Bioorganic & Medicinal Chemistry Letters 2007 17:6378-6382 DOI:10.1016/j.bmcl.2007.08.054 PMID:17911023
- Lansing, T. J., McConnell, R. T., Duckett, D. R., Spehar, G. M., Knick, V. B., Hassler, D. F., Noro, N., Furuta, M., Emmitte, K. A., Gilmer, T. M., Mook, R. A., Cheung, M. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1 Molecular Cancer Therapeutics 2007 6:450-459 DOI:10.1158/1535-7163.mct-06-0543 PMID:17267659
- Rech, J. C., Yato, M., Duckett, D., Ember, B., LoGrasso, P. V., Bergman, R. G., Ellman, J. A. Synthesis of potent bicyclic bisarylimidazole c-jun N-terminal kinase inhibitors by catalytic C-H bond activation Journal of the American Chemical Society 2007 129:490-491 DOI:10.1021/ja0676004 PMID:17227002 PMCID:PMC2556147
- Duckett, D. R., Bronstein, S. M., Taya, Y., Modrich, P. hMutS alpha- and hMutL alpha-dependent phosphorylation of p53 in response to DNA methylator damage Proceedings of the National Academy of Sciences of the United States of America 1999 96:12384-12388 DOI:10.1073/pnas.96.22.12384 PMID:10535931
- Walter, F., Murchie, A. I. H., Duckett, D. R., Lilley, D. M. J. Global structure of four-way RNA junctions studied using fluorescence resonance energy transfer RNA-a Publication of the RNA Society 1998 4:719-728 DOI:10.1017/s135583829898030x PMID:9622130
- Duckett, D. R., Murchie, A. I. H., Clegg, R. M., Bassi, G. S., Giraud-Panis, M. J. E., Lilley, D. M. J. Nucleic acid structure and recognition Biophysical Chemistry 1997 68:53-62 DOI:10.1016/s0301-4622(97)00007-0 PMID:17029905
- Mu, D., Tursun, M., Duckett, D. R., Drummond, J. T., Modrich, P., Sancar, A. Recognition and repair of compound DNA lesions (base damage and mismatch) by human mismatch repair and excision repair systems Molecular and Cellular Biology 1997 17:760-769 PMID:9001230 PMCID:PMC231802
- Duckett, D. R., Drummond, J. T., Murchie, A. I. H., Reardon, J. T., Sancar, A., Lilley, D. M., Modrich, P. Human muts alpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct Proceedings of the National Academy of Sciences of the United States of America 1996 93:6443-6447 DOI:10.1073/pnas.93.13.6443 PMID:8692834
- Duckett, D. R., Murchie, A. I. H., Lilley, D. M. J. The global folding of 4-way helical junctions in RNA, including that in U1 snRNA Cell 1995 83:1027-1036 DOI:10.1016/0092-8674(95)90218-x PMID:8521503
- Giraudpanis, M. J. E., Duckett, D. R., Lilley, D. M. J. The modular character of a DNA junction-resolving enzyme - a zinc-binding motif in bacteriophage-T4 endonuclease-VII Journal of Molecular Biology 1995 252:596-610 DOI:10.1006/jmbi.1995.0523 PMID:7563077
- Duckett, D. R., Panis, Mjeg, Lilley, D. M. J. Binding of the junction-resolving enzyme bacteriophage-T7 endonuclease-I to DNA - separation of binding and catalysis by mutation Journal of Molecular Biology 1995 246:95-107 DOI:10.1006/jmbi.1994.0069 PMID:7853409
- Duckett, D. R., Murchie, A. I. H., Giraudpanis, M. J. E., Pohler, J. R., Lilley, D. M. J. Structure of the four-way DNA junction and its interaction with proteins Philosophical Transactions of the Royal Society of London Series B-Biological Sciences 1995 347:27-36 DOI:10.1098/rstb.1995.0005 PMID:7746850
- Pohler, J. R. G., Duckett, D. R., Lilley, D. M. J. Structure of four-way DNA junctions containing a nick in one strand Journal of Molecular Biology 1994 238:62-74 DOI:10.1006/jmbi.1994.1268 PMID:8145257
- Welch, J. B., Duckett, D. R., Lilley, D. M. J. Structures of bulged three-way DNA junctions Nucleic Acids Research 1993 21:4548-4555 DOI:10.1093/nar/21.19.4548 PMID:8233789
- Lilley, D. M. J., Bhattacharyya, A., McAteer, S. P., Duckett, D. R. Gel-electrophoretic analysis of the structure of nucleic-acids Biochemical Society Transactions 1993 21:111-116 PMID:7680620
- Duckett, D. R., Murchie, A. I. H., Bhattacharyya, A., Clegg, R. M., Diekmann, S., Vonkitzing, E., Lilley, D. M. J. The structure of DNA junctions and their interaction with enzymes European Journal of Biochemistry 1992 207:285-295 DOI:10.1111/j.1432-1033.1992.tb17049.x PMID:8425539
- Duckett, D. R., Lilley, D. M. J. Effects of base mismatches on the structure of the four-way DNA junction Journal of Molecular Biology 1991 221:147-161 DOI:10.1016/0022-2836(91)90811-j PMID:1920402
- Duckett, D. R., Lilley, D. M. J. The three-way DNA junction is a Y-shaped molecule in which there is no helix-helix stacking EMBO Journal 1990 9:1659-1664 PMID:2328731 PMCID:PMC551862
- Duckett, D. R., Murchie, A. I. H., Lilley, D. M. J. The role of metal-ions in the conformation of the four-way DNA junction EMBO Journal 1990 9:583-590 PMID:2303044 PMCID:PMC551705
- Murchie, A. I. H., Clegg, R. M., Vonkitzing, E., Duckett, D. R., Diekmann, S., Lilley, D. M. J. Fluorescence energy-transfer shows that the four-way DNA junction is a right-handed cross of antiparallel molecules Nature 1989 341:763-766 DOI:10.1038/341763a0 PMID:2797209
- Duckett, D. R., Murchie, A. I. H., Diekmann, S., Vonkitzing, E., Kemper, B., Lilley, D. M. J. The structure of the Holliday junction, and its resolution Cell 1988 55:79-89 DOI:10.1016/0092-8674(88)90011-6 PMID:3167979

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