Theodore Kamenecka

Theodore Kamenecka, Ph.D.

Sr. Scientific Director, Department Of Molecular Medicine

Department: SR-MM-KAMENECKA LAB
Business Phone: (561) 228-2207
Business Email: t.kamenecka@ufl.edu

About Theodore Kamenecka

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

Research Profile

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 receptors, GPCR’s, ion channels, kinases and mitochondria for the therapeutic treatment of addiction, diabetes and obesity, multiple sclerosis, cognitive health and aging. 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.

Open Researcher and Contributor ID (ORCID)

0000-0002-3077-0167

Publications

2022
High throughput screening for compounds to the orphan nuclear receptor NR2F6.
SLAS discovery : advancing life sciences R & D. 27(4):242-248 [DOI] 10.1016/j.slasd.2022.03.005. [PMID] 35331960.
2022
REV-ERBα regulates age-related and oxidative stress-induced degeneration in retinal pigment epithelium via NRF2.
Redox biology. 51 [DOI] 10.1016/j.redox.2022.102261. [PMID] 35176707.
2022
Synthesis and structure activity relationship of the first class of LXR inverse agonists.
Bioorganic chemistry. 119 [DOI] 10.1016/j.bioorg.2021.105540. [PMID] 34902646.
2021
Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling.
Nature chemical biology. 17(3):307-316 [DOI] 10.1038/s41589-020-00719-w. [PMID] 33510451.
2021
Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism.
Science advances. 7(5) [DOI] 10.1126/sciadv.abe5504. [PMID] 33571132.
2021
Conformational Changes of RORγ During Response Element Recognition and Coregulator Engagement.
Journal of molecular biology. 433(22) [DOI] 10.1016/j.jmb.2021.167258. [PMID] 34547329.
2021
Correction to Assessment of NR4A Ligands That Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1
Journal of Medicinal Chemistry. 64(8):5216-5220 [DOI] 10.1021/acs.jmedchem.1c00526.
2021
Discovery of Selective Inhibitors for In Vitro and In Vivo Interrogation of Skeletal Myosin II
ACS Chemical Biology. 16(11):2164-2173 [DOI] 10.1021/acschembio.1c00067.
2021
Genetic and pharmacological inhibition of the nuclear receptor RORα regulates TH17 driven inflammatory disorders.
Nature communications. 12(1) [DOI] 10.1038/s41467-020-20385-9. [PMID] 33397953.
2021
Novel small molecule inhibition of IKK/NF-κB activation reduces markers of senescence and improves healthspan in mouse models of aging.
Aging cell. 20(12) [DOI] 10.1111/acel.13486. [PMID] 34734460.
2021
Structure–Activity Relationship and Biological Investigation of SR18292 (16), a Suppressor of Glucagon-Induced Glucose Production
Journal of Medicinal Chemistry. 64(2):980-990 [DOI] 10.1021/acs.jmedchem.0c01450. [PMID] 33434430.
2020
A simple and robust cell-based assay for the discovery of novel cytokinesis inhibitors.
Journal of biological methods. 7(3) [DOI] 10.14440/jbm.2020.335. [PMID] 33204739.
2020
Assessment of NR4A Ligands That Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1
Journal of Medicinal Chemistry. 63(24):15639-15654 [DOI] 10.1021/acs.jmedchem.0c00894. [PMID] 33289551.
2020
Methamphetamine Learning Induces Persistent and Selective Nonmuscle Myosin II-Dependent Spine Motility in the Basolateral Amygdala.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 40(13):2695-2707 [DOI] 10.1523/JNEUROSCI.2182-19.2020. [PMID] 32066582.
2020
Neuron-based high-content assay and screen for CNS active mitotherapeutics.
Science advances. 6(2) [DOI] 10.1126/sciadv.aaw8702. [PMID] 31934620.
2020
Pharmacological modulation and genetic deletion of REV-ERBα and REV-ERBβ regulates dendritic cell development
Biochemical and Biophysical Research Communications. 527(4):1000-1007 [DOI] 10.1016/j.bbrc.2020.05.012. [PMID] 32439175.
2020
Promoting activity of (α4)3(β2)2 nicotinic cholinergic receptors reduces ethanol consumption.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 45(2):301-308 [DOI] 10.1038/s41386-019-0475-8. [PMID] 31394567.
2019
Correction: HDX-MS reveals structural determinants for RORγ hyperactivation by synthetic agonists.
eLife. 8 [DOI] 10.7554/eLife.52847. [PMID] 31625909.
2019
Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ.
Nature communications. 10(1) [DOI] 10.1038/s41467-019-13768-0. [PMID] 31862968.
2019
Discovery and Optimization of a Series of Sulfonamide Inverse Agonists for the Retinoic Acid Receptor-Related Orphan Receptor-α.
Medicinal chemistry (Shariqah (United Arab Emirates)). 15(6):676-684 [DOI] 10.2174/1573406415666190222124745. [PMID] 30799793.
2019
Discovery of an intrasubunit nicotinic acetylcholine receptor-binding site for the positive allosteric modulator Br-PBTC.
The Journal of biological chemistry. 294(32):12132-12145 [DOI] 10.1074/jbc.RA118.006253. [PMID] 31221718.
2019
Habenular TCF7L2 links nicotine addiction to diabetes.
Nature. 574(7778):372-377 [DOI] 10.1038/s41586-019-1653-x. [PMID] 31619789.
2019
HDX-MS reveals structural determinants for RORγ hyperactivation by synthetic agonists.
eLife. 8 [DOI] 10.7554/eLife.47172. [PMID] 31172947.
2019
Native Directed Site-Selective δ-C(sp3)–H and δ-C(sp2)–H Arylation of Primary Amines
ACS Catalysis. 9(6):4887-4891 [DOI] 10.1021/acscatal.8b04927.
2019
Quantitative structural assessment of graded receptor agonism
Proceedings of the National Academy of Sciences. 116(44):22179-22188 [DOI] 10.1073/pnas.1909016116. [PMID] 31611383.
2019
The nuclear receptor REV-ERBα modulates Th17 cell-mediated autoimmune disease.
Proceedings of the National Academy of Sciences of the United States of America. 116(37):18528-18536 [DOI] 10.1073/pnas.1907563116. [PMID] 31455731.
2019
Unique Polypharmacology Nuclear Receptor Modulator Blocks Inflammatory Signaling Pathways
ACS Chemical Biology. 14(5):1051-1062 [DOI] 10.1021/acschembio.9b00236.
2018
A structural mechanism for directing corepressor-selective inverse agonism of PPARγ.
Nature communications. 9(1) [DOI] 10.1038/s41467-018-07133-w. [PMID] 30409975.
2018
Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and nociception.
Proceedings of the National Academy of Sciences of the United States of America. 115(29):E6937-E6945 [DOI] 10.1073/pnas.1803389115. [PMID] 29967167.
2018
Chemical Crosslinking Mass Spectrometry Reveals the Conformational Landscape of the Activation Helix of PPARγ; a Model for Ligand-Dependent Antagonism.
Structure (London, England : 1993). 26(11):1431-1439.e6 [DOI] 10.1016/j.str.2018.07.007. [PMID] 30146169.
2018
Defining a conformational ensemble that directs activation of PPARγ.
Nature communications. 9(1) [DOI] 10.1038/s41467-018-04176-x. [PMID] 29728618.
2018
Design, synthesis, and evaluation of simple phenol amides as ERRγ agonists.
Bioorganic & medicinal chemistry letters. 28(8):1313-1319 [DOI] 10.1016/j.bmcl.2018.03.019. [PMID] 29548571.
2018
Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation.
PLoS biology. 16(6) [DOI] 10.1371/journal.pbio.2004663. [PMID] 29889904.
2018
Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues that Stimulate Mitochondrial Respiration
Journal of Medicinal Chemistry. 61(7):3224-3230 [DOI] 10.1021/acs.jmedchem.8b00029. [PMID] 29533650.
2018
Identification of an aminothiazole series of RORβ modulators.
Bioorganic & medicinal chemistry letters. 28(7):1178-1181 [DOI] 10.1016/j.bmcl.2018.03.001. [PMID] 29534930.
2018
Identification of potent RORβ modulators: Scaffold variation.
Bioorganic & medicinal chemistry letters. 28(19):3210-3215 [DOI] 10.1016/j.bmcl.2018.08.017. [PMID] 30143422.
2018
Noncanonical agonist PPARγ ligands 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. 115(3):561-566 [DOI] 10.1073/pnas.1717776115. [PMID] 29295932.
2018
PPARγ in Complex with an Antagonist and Inverse Agonist: a Tumble and Trap Mechanism of the Activation Helix.
iScience. 5:69-79 [DOI] 10.1016/j.isci.2018.06.012. [PMID] 30123887.
2018
REV-ERBα Regulates TH17 Cell Development and Autoimmunity.
Cell reports. 25(13):3733-3749.e8 [DOI] 10.1016/j.celrep.2018.11.101. [PMID] 30590045.
2018
REV-ERBβ is required to maintain normal wakefulness and the wake-inducing effect of dual REV-ERB agonist SR9009.
Biochemical pharmacology. 150:1-8 [DOI] 10.1016/j.bcp.2018.01.009. [PMID] 29355503.
2018
Site-Selective γ-C(sp3)−H and γ-C(sp2)−H Arylation of Free Amino Esters Promoted by a Catalytic Transient Directing Group
Chemistry – A European Journal. 24(38):9535-9541 [DOI] 10.1002/chem.201802465.
2018
Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.
Molecular metabolism. 9:28-42 [DOI] 10.1016/j.molmet.2018.01.017. [PMID] 29428596.
2018
Structural and Dynamic Elucidation of a Non-acid PPARγ Partial Agonist: SR1988.
Nuclear receptor research. 5 [DOI] 10.11131/2018/101350. [PMID] 30906767.
2017
GLP-1 acts on habenular avoidance circuits to control nicotine intake.
Nature neuroscience. 20(5):708-716 [DOI] 10.1038/nn.4540. [PMID] 28368384.
2017
Modification of the Orthosteric PPARγ Covalent Antagonist Scaffold Yields an Improved Dual-Site Allosteric Inhibitor.
ACS chemical biology. 12(4):969-978 [DOI] 10.1021/acschembio.6b01015. [PMID] 28165718.
2017
RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 31(10):4492-4502 [DOI] 10.1096/fj.201700172R. [PMID] 28646017.
2017
Selective Chemical Inhibition of PGC-1α Gluconeogenic Activity Ameliorates Type 2 Diabetes.
Cell. 169(1):148-160.e15 [DOI] 10.1016/j.cell.2017.03.001. [PMID] 28340340.
2017
Structure-Activity Relationship of 2,4-Dichloro-N-(3,5-dichloro-4-(quinolin-3-yloxy)phenyl)benzenesulfonamide (INT131) Analogs for PPARγ-Targeted Antidiabetics.
Journal of medicinal chemistry. 60(11):4584-4593 [DOI] 10.1021/acs.jmedchem.6b01727. [PMID] 28485590.
2017
Synthesis of novel steroidal agonists, partial agonists, and antagonists for the glucocorticoid receptor.
Bioorganic & medicinal chemistry letters. 27(2):347-353 [DOI] 10.1016/j.bmcl.2016.11.007. [PMID] 27919657.
2016
Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis.
The Journal of clinical investigation. 126(11):4273-4288 [DOI] 10.1172/JCI85510. [PMID] 27701146.
2016
Correction: Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression.
PloS one. 11(5) [DOI] 10.1371/journal.pone.0156367. [PMID] 27195801.
2016
Multigram-scale Synthesis of Enantiopure 3,3-Difluoroproline.
Tetrahedron letters. 57(50):5658-5660 [DOI] 10.1016/j.tetlet.2016.11.012. [PMID] 28584384.
2016
N-Arylsulfonyl Indolines as Retinoic Acid Receptor-Related Orphan Receptor γ (RORγ) Agonists.
ChemMedChem. 11(23):2607-2620 [DOI] 10.1002/cmdc.201600491. [PMID] 27879053.
2016
Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation.
PloS one. 11(9) [DOI] 10.1371/journal.pone.0162452. [PMID] 27603791.
2016
PPARG Post-translational Modifications Regulate Bone Formation and Bone Resorption.
EBioMedicine. 10:174-84 [DOI] 10.1016/j.ebiom.2016.06.040. [PMID] 27422345.
2016
Probing the Complex Binding Modes of the PPARγ Partial Agonist 2-Chloro-N-(3-chloro-4-((5-chlorobenzo[d]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide (T2384) to Orthosteric and Allosteric Sites with NMR Spectroscopy.
Journal of medicinal chemistry. 59(22):10335-10341 [DOI] 10.1021/acs.jmedchem.6b01340. [PMID] 27783520.
2016
SR2067 Reveals a Unique Kinetic and Structural Signature for PPARγ Partial Agonism.
ACS chemical biology. 11(1):273-83 [DOI] 10.1021/acschembio.5b00580. [PMID] 26579553.
2016
Synthesis of 2-aryl-2H-tetrazoles via a regioselective [3+2] cycloaddition reaction.
Tetrahedron letters. 57(14):1597-1599 [PMID] 27041776.
2016
Synthetic RORγt Agonists Enhance Protective Immunity.
ACS chemical biology. 11(4):1012-8 [DOI] 10.1021/acschembio.5b00899. [PMID] 26785144.
2016
The Methionine Transamination Pathway Controls Hepatic Glucose Metabolism through Regulation of the GCN5 Acetyltransferase and the PGC-1α Transcriptional Coactivator.
The Journal of biological chemistry. 291(20):10635-45 [DOI] 10.1074/jbc.M115.706200. [PMID] 27022023.
2016
The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.
Cell. 166(2):424-435 [DOI] 10.1016/j.cell.2016.05.071. [PMID] 27374330.
2016
TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway.
Molecular metabolism. 5(10):903-917 [DOI] 10.1016/j.molmet.2016.08.008. [PMID] 27689003.
2016
Unorthodox Acetylcholine Binding Sites Formed by α5 and β3 Accessory Subunits in α4β2* Nicotinic Acetylcholine Receptors.
The Journal of biological chemistry. 291(45):23452-23463 [PMID] 27645992.
2015
A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit.
The Journal of biological chemistry. 290(48):28834-46 [DOI] 10.1074/jbc.M115.676551. [PMID] 26432642.
2015
An Accessory Agonist Binding Site Promotes Activation of α4β2* Nicotinic Acetylcholine Receptors.
The Journal of biological chemistry. 290(22):13907-18 [DOI] 10.1074/jbc.M115.646786. [PMID] 25869137.
2015
Antiobesity Effect of a Small Molecule Repressor of RORγ.
Molecular pharmacology. 88(1):48-56 [DOI] 10.1124/mol.114.097485. [PMID] 25904554.
2015
Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis.
Cancer cell. 28(1):42-56 [DOI] 10.1016/j.ccell.2015.05.007. [PMID] 26120082.
2015
Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists.
ACS medicinal chemistry letters. 6(9):998-1003 [DOI] 10.1021/acsmedchemlett.5b00218. [PMID] 26396687.
2015
Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation.
Proceedings of the National Academy of Sciences of the United States of America. 112(33):10401-6 [DOI] 10.1073/pnas.1504387112. [PMID] 26243880.
2015
Pharmacological repression of PPARγ promotes osteogenesis.
Nature communications. 6 [DOI] 10.1038/ncomms8443. [PMID] 26068133.
2015
ROR inverse agonist suppresses insulitis and prevents hyperglycemia in a mouse model of type 1 diabetes.
Endocrinology. 156(3):869-81 [DOI] 10.1210/en.2014-1677. [PMID] 25560829.
2015
Structural mechanism for signal transduction in RXR nuclear receptor heterodimers.
Nature communications. 6 [DOI] 10.1038/ncomms9013. [PMID] 26289479.
2015
Suppression of atherosclerosis by synthetic REV-ERB agonist.
Biochemical and biophysical research communications. 460(3):566-71 [DOI] 10.1016/j.bbrc.2015.03.070. [PMID] 25800870.
2014
An alternate binding site for PPARγ ligands.
Nature communications. 5 [DOI] 10.1038/ncomms4571. [PMID] 24705063.
2014
Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area.
Proceedings of the National Academy of Sciences of the United States of America. 111(16):E1648-55 [DOI] 10.1073/pnas.1315542111. [PMID] 24706819.
2014
Pharmacologic repression of retinoic acid receptor-related orphan nuclear receptor γ is therapeutic in the collagen-induced arthritis experimental model.
Arthritis & rheumatology (Hoboken, N.J.). 66(3):579-88 [DOI] 10.1002/art.38272. [PMID] 24574218.
2014
Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour.
Nature communications. 5 [DOI] 10.1038/ncomms6759. [PMID] 25536025.
2014
Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors.
Bioorganic & medicinal chemistry letters. 24(2):674-8 [DOI] 10.1016/j.bmcl.2013.11.049. [PMID] 24365158.
2014
Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors.
Bioorganic & medicinal chemistry letters. 24(1):161-4 [DOI] 10.1016/j.bmcl.2013.11.052. [PMID] 24332487.
2014
The discovery of indole full agonists of the neurotensin receptor 1 (NTSR1).
Bioorganic & medicinal chemistry letters. 24(16):3974-8 [DOI] 10.1016/j.bmcl.2014.06.033. [PMID] 24997685.
2013
A liver-selective LXR inverse agonist that suppresses hepatic steatosis.
ACS chemical biology. 8(3):559-67 [DOI] 10.1021/cb300541g. [PMID] 23237488.
2013
Design and synthesis of 1-aryl-5-anilinoindazoles as c-Jun N-terminal kinase inhibitors.
Bioorganic & medicinal chemistry letters. 23(9):2683-7 [DOI] 10.1016/j.bmcl.2013.02.082. [PMID] 23518277.
2013
Development of a high-throughput screening-compatible cell-based functional assay to identify small molecule probes of the galanin 3 receptor (GalR3).
Assay and drug development technologies. 11(8):468-77 [DOI] 10.1089/adt.2013.526. [PMID] 24116939.
2013
Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy.
Nature medicine. 19(8):1039-46 [DOI] 10.1038/nm.3213. [PMID] 23852339.
2013
Small molecule amides as potent ROR-γ selective modulators.
Bioorganic & medicinal chemistry letters. 23(2):532-6 [DOI] 10.1016/j.bmcl.2012.11.025. [PMID] 23232056.
2012
Discovery of a highly selective CYP3A4 inhibitor suitable for reaction phenotyping studies and differentiation of CYP3A4 and CYP3A5.
Drug metabolism and disposition: the biological fate of chemicals. 40(9):1803-9 [DOI] 10.1124/dmd.112.046144. [PMID] 22696420.
2012
Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists.
Bioorganic & medicinal chemistry letters. 22(12):3890-4 [DOI] 10.1016/j.bmcl.2012.04.122. [PMID] 22617492.
2012
Identification of a selective RORγ ligand that suppresses T(H)17 cells and stimulates T regulatory cells.
ACS chemical biology. 7(9):1515-9 [PMID] 22769242.
2012
Identification of SR2211: a potent synthetic RORγ-selective modulator.
ACS chemical biology. 7(4):672-7 [DOI] 10.1021/cb200496y. [PMID] 22292739.
2012
Imidazopyridines as selective CYP3A4 inhibitors.
Bioorganic & medicinal chemistry letters. 22(4):1611-4 [DOI] 10.1016/j.bmcl.2011.12.125. [PMID] 22264486.
2012
Ligand and receptor dynamics contribute to the mechanism of graded PPARγ agonism.
Structure (London, England : 1993). 20(1):139-50 [DOI] 10.1016/j.str.2011.10.018. [PMID] 22244763.
2012
LXR-mediated inhibition of CD4+ T helper cells.
PloS one. 7(9) [DOI] 10.1371/journal.pone.0046615. [PMID] 23029557.
2012
Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.
Nature. 485(7396):62-8 [DOI] 10.1038/nature11030. [PMID] 22460951.
2012
Small molecule tertiary amines as agonists of the nuclear hormone receptor Rev-erbα.
Bioorganic & medicinal chemistry letters. 22(13):4413-7 [DOI] 10.1016/j.bmcl.2012.04.126. [PMID] 22633688.
2012
Synthesis and SAR of tetrahydroisoquinolines as Rev-erbα agonists.
Bioorganic & medicinal chemistry letters. 22(11):3739-42 [DOI] 10.1016/j.bmcl.2012.04.023. [PMID] 22560469.
2012
TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis.
Cell. 151(1):96-110 [DOI] 10.1016/j.cell.2012.08.034. [PMID] 23021218.
2011
Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation.
Nature. 477(7365):477-81 [DOI] 10.1038/nature10383. [PMID] 21892191.
2011
Identification of a novel non-retinoid pan inverse agonist of the retinoic acid receptors.
ACS chemical biology. 6(6):618-27 [DOI] 10.1021/cb100396s. [PMID] 21381756.
2011
Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB.
ACS chemical biology. 6(2):131-4 [DOI] 10.1021/cb1002575. [PMID] 21043485.
2011
Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand.
Nature. 472(7344):491-4 [DOI] 10.1038/nature10075. [PMID] 21499262.
2011
Synthesis and SAR of 2-phenoxypyridines as novel c-Jun N-terminal kinase inhibitors.
Bioorganic & medicinal chemistry letters. 21(23):7072-5 [DOI] 10.1016/j.bmcl.2011.09.090. [PMID] 22004719.
2011
Synthesis and SAR of 4-(pyrazol-3-yl)-pyridines as novel c-jun N-terminal kinase inhibitors.
Bioorganic & medicinal chemistry letters. 21(9):2732-5 [DOI] 10.1016/j.bmcl.2010.11.104. [PMID] 21185177.
2011
Synthesis and SAR of novel quinazolines as potent and brain-penetrant c-jun N-terminal kinase (JNK) inhibitors.
Bioorganic & medicinal chemistry letters. 21(6):1719-23 [DOI] 10.1016/j.bmcl.2011.01.079. [PMID] 21316221.
2010
Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5.
Nature. 466(7305):451-6 [DOI] 10.1038/nature09291. [PMID] 20651683.
2010
Cytochrome P450-mediated bioactivation of the epidermal growth factor receptor inhibitor erlotinib to a reactive electrophile.
Drug metabolism and disposition: the biological fate of chemicals. 38(7):1238-45 [DOI] 10.1124/dmd.109.030361. [PMID] 20382753.
2010
Regulation of adipogenesis by natural and synthetic REV-ERB ligands.
Endocrinology. 151(7):3015-25 [DOI] 10.1210/en.2009-0800. [PMID] 20427485.
2009
Bioactivation of the epidermal growth factor receptor inhibitor gefitinib: implications for pulmonary and hepatic toxicities.
Chemical research in toxicology. 22(10):1736-42 [DOI] 10.1021/tx900256y. [PMID] 19803472.
2009
Efficient methodology for the synthesis of 3-amino-1,2,4-triazoles.
The Journal of organic chemistry. 74(19):7595-7 [DOI] 10.1021/jo9016502. [PMID] 19731897.
2009
Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors.
Bioorganic & medicinal chemistry letters. 19(12):3344-7 [DOI] 10.1016/j.bmcl.2009.03.086. [PMID] 19433357.
2008
Inhibitors of c-jun-N-terminal kinase (JNK).
Mini reviews in medicinal chemistry. 8(8):755-66 [PMID] 18673131.
2008
Insular hypocretin transmission regulates nicotine reward.
Proceedings of the National Academy of Sciences of the United States of America. 105(49):19480-5 [DOI] 10.1073/pnas.0808023105. [PMID] 19033203.
2008
Transposition of three amino acids transforms the human metabotropic glutamate receptor (mGluR)-3-positive allosteric modulation site to mGluR2, and additional characterization of the mGluR2-positive allosteric modulation site.
The Journal of pharmacology and experimental therapeutics. 326(1):240-51 [DOI] 10.1124/jpet.108.138271. [PMID] 18430863.
2007
3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors.
Bioorganic & medicinal chemistry letters. 17(22):6378-82 [PMID] 17911023.
2007
Partial agonists activate PPARgamma using a helix 12 independent mechanism.
Structure (London, England : 1993). 15(10):1258-71 [PMID] 17937915.
2005
Benzazoles as allosteric potentiators of metabotropic glutamate receptor 2 (mGluR2): efficacy in an animal model for schizophrenia.
Bioorganic & medicinal chemistry letters. 15(18):4068-72 [PMID] 16005222.
2005
Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor.
Bioorganic & medicinal chemistry letters. 15(19):4354-8 [PMID] 16046122.
2005
Dipyridyl amides: potent metabotropic glutamate subtype 5 (mGlu5) receptor antagonists.
Bioorganic & medicinal chemistry letters. 15(4):1197-200 [PMID] 15686941.
2005
Dipyridyl amines: potent metabotropic glutamate subtype 5 receptor antagonists.
Bioorganic & medicinal chemistry letters. 15(19):4350-3 [PMID] 16039855.
2004
5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,3′-bipyridine: a highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity.
Bioorganic & medicinal chemistry letters. 14(15):3993-6 [PMID] 15225713.
2004
Amidines as amide bond replacements in VLA-4 antagonists.
Bioorganic & medicinal chemistry letters. 14(9):2323-6 [PMID] 15081033.
2004
Bioisosteric replacement of anilide with benzoxazole: potent and orally bioavailable antagonists of VLA-4.
Bioorganic & medicinal chemistry letters. 14(9):2331-4 [PMID] 15081035.
2003
N-(3-phenylsulfonyl-3-piperidinoyl)-phenylalanine derivatives as potent, selective VLA-4 antagonists.
Bioorganic & medicinal chemistry letters. 13(5):885-90 [PMID] 12617914.
2002
Construction of substituted cyclohexanones by reductive cyclization of 7-oxo-2,8-alkadienyl esters.
Organic letters. 4(1):79-82 [PMID] 11772095.
2002
N-(arylacetyl)-biphenylalanines as potent VLA-4 antagonists.
Bioorganic & medicinal chemistry letters. 12(16):2141-4 [PMID] 12127523.
2002
N-aryl 2,6-dimethoxybiphenylalanine analogues as VLA-4 antagonists.
Bioorganic & medicinal chemistry letters. 12(5):729-31 [PMID] 11858990.
2002
N-aryl-prolyl-dipeptides as potent antagonists of VLA-4.
Bioorganic & medicinal chemistry letters. 12(16):2205-8 [PMID] 12127538.
2002
The discovery of acylated beta-amino acids as potent and orally bioavailable VLA-4 antagonists.
Bioorganic & medicinal chemistry letters. 12(4):611-4 [PMID] 11844683.
2001
Discovery through total synthesis: a retrospective on the himastatin problem.
Chemistry (Weinheim an der Bergstrasse, Germany). 7(1):41-63 [PMID] 11205026.
2001
The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.
Bioorganic & medicinal chemistry letters. 11(20):2709-13 [PMID] 11591507.
1998
Studies in the Total Synthesis of Himastatin: A Revision of the Stereochemical Assignment.
Angewandte Chemie (International ed. in English). 37(21):2993-2995 [DOI] 10.1002/(SICI)1521-3773(19981116)37:21<2993::AID-ANIE2993>3.0.CO;2-I. [PMID] 29711127.
1998
Total Synthesis of Himastatin: Confirmation of the Revised Stereostructure.
Angewandte Chemie (International ed. in English). 37(21):2995-2998 [DOI] 10.1002/(SICI)1521-3773(19981116)37:21<2995::AID-ANIE2995>3.0.CO;2-6. [PMID] 29711142.
Assessment of NR4A Ligands that Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1
. [DOI] 10.1101/2020.05.22.109017.
Conformational Changes of RORγ During Response Element Recognition and Coregulator Engagement
. [DOI] 10.1101/2021.05.25.445650.
Quantitative Structural Assessment of Graded Receptor Agonism
. [DOI] 10.1101/617100.

Grants

Sep 2022 ACTIVE
Mitochondrial therapeutics for healthy brain aging
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Sep 2022 ACTIVE
Tissue Selective Glucocorticoids
Role: Co-Investigator
Funding: NATL INST OF HLTH NIGMS
Apr 2022 ACTIVE
Molecular basis of activation of the orphan nuclear receptor Nurr1
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Apr 2022 ACTIVE
Targeting Go and Grow in Glioblastoma
Role: Project Manager
Funding: MAYO CLINIC via NATL INST OF HLTH NINDS
Apr 2022 ACTIVE
Small molecules targeting hepatic glucose production and insulin resistance
Role: Co-Investigator
Funding: DANA FARBER CANCER INST via NATL INST OF HLTH NIDDK
Apr 2022 ACTIVE
Targeting Cellular Senescence to Extend Healthspan
Role: Principal Investigator
Funding: MAYO CLINIC via NATL INST OF HLTH NIA
Apr 2022 ACTIVE
Developing nonmuscle myosin II inhibitors for the treatment of glioblastoma
Role: Co-Investigator
Funding: NATL INST OF HLTH NINDS
Apr 2022 ACTIVE
Mechanistic studies of corepressor-mediated PPAR? transcriptional repression
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDDK
Apr 2022 ACTIVE
Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for Glioblastoma
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Apr 2022 ACTIVE
Development of novel therapeutics for opioid dependence
Role: Principal Investigator
Funding: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI via NATL INST OF HLTH NIDA
Apr 2022 ACTIVE
Identification of REV-ERB inverse agonists for cancer immunotherapy
Role: Co-Investigator
Funding: NATL INST OF HLTH NCI
Apr 2022 – Sep 2022
Parallel Multimodal High-throughput screening to identify activators of the orexin receptors
Role: Principal Investigator
Funding: NATL INST OF HLTH NIMH
Apr 2022 – Aug 2022
Mitochondrial therapeutics for healthy brain aging
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Apr 2022 – Jul 2022
Optimization of SR1903 and SR10171
Role: Co-Project Director/Principal Investigator
Funding: SYNKINE THERAPEUTICS
Apr 2022 – Jun 2022
ALDH1a1 Inhibition As A Therapeutic Target In Visceral Adiposity and Type 2 Diabetes
Role: Co-Project Director/Principal Investigator
Funding: BRIGHAM AND WOMENS HOSPITAL via NATL INST OF HLTH NIDDK
Apr 2022 – May 2022
Identification of Chemical Probes for the Orphan Nuclear Receptor NR2F6
Role: Co-Investigator
Funding: NATL INST OF HLTH NCI

Education

Post-doctorate
1996-1998 · Memorial Sloan Kettering Cancer Center
Ph.D. in Chemistry
1990-1996 · University of California, Irvine
Bachelor of Science in Chemistry
1986-1990 · University of Rochester

Contact Details

Phones:
Business:
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