A5009016034- Receptor Mechanisms and Signaling
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Bioactive Natural Diterpenoids Research
- Neurotransmitter Receptor Influence on Behavior
- Monoclonal and Polyclonal Antibodies Research
- Crystallography and molecular interactions
- Breast Cancer Treatment Studies
- Chemical synthesis and alkaloids
- Computational Drug Discovery Methods
- HER2/EGFR in Cancer Research
- Cancer-related Molecular Pathways
- Plant-based Medicinal Research
- Phosphodiesterase function and regulation
- Cytokine Signaling Pathways and Interactions
- Chemical Synthesis and Analysis
- Nicotinic Acetylcholine Receptors Study
- Bioactive Compounds and Antitumor Agents
- Cyclization and Aryne Chemistry
- Electron Spin Resonance Studies
- Catalytic Alkyne Reactions
- Synthesis and biological activity
- Cell death mechanisms and regulation
- Pharmacological Receptor Mechanisms and Effects
- Pelvic floor disorders treatments
John Sealy Hospital
2024
The University of Texas Medical Branch at Galveston
2014-2023
San Jacinto College
2019
Galveston College
2014
The University of Texas MD Anderson Cancer Center
2013
California State University, Northridge
2008-2010
University of Leeds
2008
Kiel University
2007
Ludwig-Maximilians-Universität München
2005
LMU Klinikum
2005
Activator protein 1 (AP-1) is a pivotal transcription factor that regulates wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports AP-1 plays an important role in several severe disorders cancer, fibrosis, organ injury, as well inflammatory such asthma, psoriasis, rheumatoid arthritis. has emerged actively pursued drug discovery target over the past decade. Excitingly, selective...
Oridonin (1), a complex ent-kaurane diterpenoid isolated from the traditional Chinese herb Isodon rubescens , has demonstrated great potential in treatment of various human cancers due to its unique and safe anticancer pharmacological profile. Nevertheless, clinical development oridonin for cancer therapy been hampered by relatively moderate potency, limited aqueous solubility, poor bioavailability. Herein, we report concise synthesis series novel nitrogen-enriched derivatives with...
Oridonin (1) has attracted considerable attention in recent years because of its unique and safe anticancer pharmacological profile. Nevertheless, it exhibits moderate to poor effects against highly aggressive cancers including triple-negative drug-resistant breast cancer cells. Herein, we report the rational design synthesis novel dienone derivatives with an additional α,β-unsaturated ketone system diversely installed A-ring based on this class natural scaffold that features dense...
Efficient and concise synthetic approaches have been developed for the rapid diverse installation of azide functionalities at C-1, C-2, or C-3 positions oridonin (1) with highly controlled regio- stereoselectivity, while keeping key reactive pharmacophores intact by utilizing unique preactivation strategies based on common synthon 4. Further functionalization these azides through click chemistry yielding triazole derivatives successfully provides access to an expanded natural scaffold-based...
A mild and concise approach for the construction of a 3,4-dihydro-2<italic>H</italic>-pyran ring integrated into A-ring natural product oridonin is reported herein.
Exchange proteins directly activated by cAMP (EPAC) as guanine nucleotide exchange factors mediate the effects of pivotal second messenger cAMP, thereby regulating a wide variety intracellular physiological and pathophysiological processes. A series novel 2-(isoxazol-3-yl)-2-oxo-N'-phenyl-acetohydrazonoyl cyanide EPAC antagonists was synthesized evaluated in an effort to optimize properties previously identified high-throughput (HTS) hit 1 (ESI-09). Structure-activity relationship (SAR)...
An impaired signaling capacity of the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) has been implicated in neurobehavioral processes that promote relapse vulnerability cocaine use disorder (CUD). Restoration diminished 5-HT2CR through positive allosteric modulation presents a novel therapeutic approach. Several new molecules with 4-alkylpiperidine-2-carboxamide scaffold were designed, synthesized, and pharmacologically evaluated, leading to discovery selective modulators (PAMs). Compound 16...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid/liquid intermolecular transfer of dynamic nuclear polarization. Enhanced flowing fluid proton NMR signals via immobilized spin labelsR. Gitti, C. Wild, Tsiao, K. Zimmer, T. E. Glass, and Harry DornCite this: J. Am. Chem. Soc. 1988, 110, 7, 2294–2296Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March...
The serotonin 5-HT
PAMs new in town! An effective, combined bioinformatics and chemoinformatics approach was applied to the design of novel asymmetric bivalent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators (PAMs) with marked potency vitro efficacy vivo for preventing neuroapoptosis. The chemotype could provide pharmacological probes potential therapeutic agents glutamatergic hypofunction its related neurological psychiatric disorders. As a service our...
Targeting the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) allosteric site to potentiate endogenous 5-HT tone may provide novel therapeutics alleviate impact of costly, chronic diseases such as obesity and substance use disorders. Expanding upon our recently described 5-HT2CR-positive modulators (PAMs) based on 4-alkylpiperidine-2-carboxamide scaffold, we optimized undecyl moiety at 4-position with variations cyclohexyl- or phenyl-containing fragments reduce rotatable bonds lipophilicity....
N,N-Diphenylamines were discovered as potent and selective EPAC2 inhibitors. A study was conducted to determine the structure–activity relationships in a series of inhibitors which several compounds displayed submicromolar potencies. Selectivity over related EPAC1 protein also demonstrated. Computational modeling reveals an allosteric site that is distinct from cAMP binding domain shared by both EPAC isoforms, providing theory with regards subtype selectivity.
Intramolecular radical cyclizations of Co2(CO)6-complexed bis-propargyl alcohols 1−5 provide an easy, two-step access to the otherwise hardly accessible d,l- and meso-3,4-diaryl-1,5-cyclodecadiynes 21−25. The acid-induced generation bis-cations 6−10 is followed by reduction with a 100-fold excess zinc, generating key reactive intermediates, i.e. cobalt-complexed radicals 11−15. substitution pattern (0-, 4-, 3,4-, 3,4,5-) nature aromatic substituents (H, i-Pr, OMe) are found essential both...
Using a cytotoxicity-based phenotypic screen of highly diverse library 20,000 small-molecule compounds, we identified quinolin-8-yl-nicotinamide, QN519, as promising lead. QN519 represents novel scaffold with drug-like properties, showing potent in vitro cytotoxicity panel 12 cancer cell lines. Subsequently, lead optimization campaign generated compounds IC50 values < 1 μM. An optimized compound, QN523, shows significant vivo efficacy pancreatic xenograft model. QN523 treatment significantly...