Theodore Kamenecka, PhD

Scientific Director, Sr
Department of Molecular Medicine
Florida Campus


Scripps Research Joint Appointments

Translational Research Institute

Research Focus

Medicinal Chemistry and Drug Discovery

The research interest in my group is in the design, synthesis and evaluation of novel compounds of biological and therapeutic interest. Currently, we are involved in the design and synthesis of novel small molecule modulators of nuclear hormone receptors, GPCR's, ion channels, and kinases for the therapeutic treatment of diabetes and obesity, sleep, schizophrenia, and addiction. Working closely with other departments such as molecular biology, pharmacology, and drug metabolism, we optimize lead compounds for potency, ADME (absorption, distribution, metabolism, and excretion), safety pharmacology, and toxicology in order to generate compounds suitable for preclinical development.


Ph.D. (Chemistry), University of California, Irvine, 1996
B.S. (Chemistry), University of Rochester, 1990

Professional Experience

2015-2017 Associate Professor of Molecular Therapeutics, Molecular Therapeutics, Scripps Research
2013-2015 Assistant Professor, Molecular Therapeutics, Scripps Research
2004-2015 Associate Scientific Director II, Translational Research Institute, Scripps Research
2004-2012 Senior Staff Scientist (Joint Appointment), Chemistry, Scripps Research

Selected References

All Publications

Strutzenberg, T. S., Garcia-Ordonez, R. D., Novick, S. J., Park, H., Chang, M. R., Doebellin, C., He, Y., Patouret, R., Kamenecka, T. M., Griffin, P. R. HDX-MS reveals structural determinants for RORy hyperactivation by synthetic agonists.  Elife  2019 8  DOI:10.7554/eLife.47172  PMID:31172947 PMCID:PMC6579513

Lin, H., Pan, X., Barsamian, A. L., Kamenecka, T. M., Bannister, T. D. Native directed site-selective delta-C(sp(3)) H and delta_C(sp(2))-H arylation of primary amines. ACS Catalysis  2019 9:4887-4891  DOI:10.1021/acscatal.8b04927

Chang, M. R., Ciesla, A., Strutzenberg, T. S., Novick, S. J., He, Y., Garcia-Ordonez, R. D., Frkic, R. L., Bruning, J. B., Kamenecka, T. M., Griffin, P. R. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways.  ACS Chemical Biology  2019 14:1051-1062  DOI:10.1021/acschembio.9b00236  PMID:30951276

Brust, R., Shang, J. S., Fuhrmann, J., Mosure, S. A., Bass, J., Cano, A., Heidari, Z., Chrisman, I. M., Nemetchek, M. D., Blayo, A. L., Griffin, P. R., Kamenecka, T. M., et al. A structural mechanism for directing corepressor-selective inverse agonism of PPARy. Nature Communications  2018 9  DOI:10.1038/s41467-018-07133-w  PMID:30409975  PMCID:PMC6224492

Zheng, J., Corzo, C., Chang, M. R., Shang, J. S., Lam, V. Q., Brust, R., Blayo, A. L., Bruning, J. B., Kamenecka, T. M., Kojetin, D. J., Griffin, P. R.  Chemical crosslinking mass spectrometry reveals the conformational landscape of the activation helix of PPARy; a model of ligand-dependent antagonism. Structure  201826:1431-1439  DOI:10.1016/j.str.2018.07.007  PMID:30146169  PMCID:PMC6221991

Shang, J., Brust, R., Mosure, S. A., Bass, J., Munoz-Tello, P., Lin, H., Hughes, T. S., Tang, M., Ge, Q., Kamenecka, T. M., Kojetin, D.  J.  Cooperative cobinding of synthetic and natural ligands to the nuclear receptor PPARy.  ELife  2018 7  DOI:10.7554/eLife.43320  PMID:30575522  PMCID:PMC6317912

Lin, H., Doebelin, C., Patouret, R., Garcia-Ordonez, R. D., Chang, M. R., Dharmarajan, V., Bayona, C. R., Cameron, M. D., Griffin, P. R., Kamenecka, T. M. Design, synthesis, and evaluation of simple phenol amides as ERRy agonists.  Bioorganic & Medicinal Chemistry Letters  2018 28:1313-1319  DOI:10.1016/j.bmcl.2018.03.019  PMID:29548571  PMCID:PMC5893368

Patouret, R., Doebelin, C., Garcia-Ordonez, R. D., Ra Chang, M., Ruiz, C., Cameron, M. D., Griffin, P. R., Kamenecka, T. M. Identification of an aminothiazole series of RORβ modulators.  Bioorganic & Medicinal Chemistry Letters  2018 28:1178-1181  DOI:10.1016/j.bmcl.2018.03.001  PMID:29534930 PMCID:PMC5859951

Doebelin, C., Patouret, R., Garcia-Ordonez, R. D., Chang, M. R., Dharmarajan, V., Novick, S., Ciesla, A., Campbell, S., Solt, L. A., Griffin, P. R., Kamenecka, T. M. Identification of potent RORβ modulators: Scaffold variation.  Bioorganic & Medicinal Chemistry Letters  2018 28:3210-3215  DOI:10.1016/j.bmcl.2018.08.017 PMID:30143422  PMCID:PMC6238650

Khandekar, M. J., Banks, A. S., Laznik-Bogoslavski, D., White, J. P., Choi, J. H., Kazak, L., Lo, J. C., Cohen, P., Wong, K. K., Kamenecka, T. M., Griffin, P. R., Spiegelman, B. M.  Noncanonical agonist PPARy lignads modulate the response to DNA damage and sensitize cancer cells to cytotoxic chemotherapy.  Proceedings of the National Academy of Sciences of the United States of America  2018 115:561-566  DOI:10.1073/pnas.1717776115  PMID:29295932  PMCID:PMC5776997

Lin, H., Wang, C., Bannister, T. D., Kamenecka, T. M.  Site-selective y-C(sp3) and y-C(sp2)-H arylation of free amino esters promoted by a catalytic transient directing group.  Chemistry-a European Journal  201824:9535-9541  DOI:10.1002/chem.201802465  PMID:29775502

Pettersson-Klein, A. T., Izadi, M., Ferreira, D. M. S., Cervenka, I., Correia, J. C., Martinez-Redondo, V., Southern, M., Cameron, M., Kamenecka, T., Agudelo, L. Z., Porsmyr-Palmertz, M., Martens, U., et al. Small molecule PGC-1x1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration. Molecular Metabolism  2018 9:28-42  DOI:10.1016/j.molmet.2018.01.017  PMID:29428596 PMCID:PMC58701

Synthesis of 2-aryl-2H-tetrazoles via a regioselective [3+2] cycloaddition reaction. Patouret R, Kamenecka TM. Tetrahedron Lett. 2016 Apr 6;57(14):1597-1599.

Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation. Sun Y, Liu CH, SanGiovanni JP, Evans LP, Tian KT, Zhang B, Stahl A, Pu WT, Kamenecka TM, Solt LA, Chen J. Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10401-6. doi: 10.1073/pnas.1504387112. Epub 2015 Aug 4.

Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists. Asteian A, Blayo AL, He Y, Koenig M, Shin Y, Kuruvilla DS, Corzo CA, Cameron MD, Lin L, Ruiz C, Khan S, Kumar N, Busby S, Marciano DP, Garcia-Ordonez RD, Griffin PR, Kamenecka TM. ACS Med Chem Lett. 2015 Aug 4;6(9):998-1003. doi: 10.1021/acsmedchemlett.5b00218. eCollection 2015 Sep 10.

Pharmacological repression of PPARγ promotes osteogenesis. Marciano DP, Kuruvilla DS, Boregowda SV, Asteian A, Hughes TS, Garcia-Ordonez R, Corzo CA, Khan TM, Novick SJ, Park H, Kojetin DJ, Phinney DG, Bruning JB, Kamenecka TM, Griffin PR. Nat Commun. 2015 Jun 12;6:7443. doi: 10.1038/ncomms8443.

An Accessory Agonist Binding Site Promotes Activation of α4β2* Nicotinic Acetylcholine Receptors. Wang J, Kuryatov A, Sriram A, Jin Z, Kamenecka TM, Kenny PJ, Lindstrom J. J Biol Chem. 2015 May 29;290(22):13907-18. doi: 10.1074/jbc.M115.646786. Epub 2015 Apr 13.