A5032673796- Synthesis and biological activity
- Synthesis and Biological Evaluation
- Receptor Mechanisms and Signaling
- Microbial Natural Products and Biosynthesis
- Multicomponent Synthesis of Heterocycles
- Chemical Synthesis and Analysis
- Chemical synthesis and alkaloids
- Pharmacological Receptor Mechanisms and Effects
- Synthetic Organic Chemistry Methods
- Synthesis and Characterization of Heterocyclic Compounds
- Traditional and Medicinal Uses of Annonaceae
- Psychedelics and Drug Studies
- Colorectal Cancer Treatments and Studies
- Protein Kinase Regulation and GTPase Signaling
- Mass Spectrometry Techniques and Applications
- Chronic Myeloid Leukemia Treatments
- Parkinson's Disease Mechanisms and Treatments
- Religious Studies and Spiritual Practices
- Angiogenesis and VEGF in Cancer
- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- DNA and Nucleic Acid Chemistry
- Material Properties and Applications
- Neurotransmitter Receptor Influence on Behavior
- Synthesis of β-Lactam Compounds
Union University
2023
Vanderbilt University Medical Center
2007-2021
Lipscomb University
2013-2021
Vanderbilt University
2007-2018
The therapeutic potential of small molecule signaling inhibitors is often limited by off-target effects. Recently, in a screen for compounds that perturb the zebrafish embryonic dorsoventral axis, we identified dorsomorphin, first selective inhibitor bone morphogenetic protein (BMP) signaling. Here show dorsomorphin has significant "off-target" effects against VEGF (vascular endothelial growth factor) type-2 receptor (Flk1/KDR) and disrupts angiogenesis. Since both BMP signals are known to...
Myeloid cell leukemia 1 (Mcl-1), a member of the Bcl-2 family proteins, is overexpressed and amplified in various cancers promotes aberrant survival tumor cells that otherwise would undergo apoptosis. Here we describe discovery potent selective Mcl-1 inhibitors using fragment-based methods structure-based design. NMR-based screening large fragment library identified two chemically distinct hit series bind to different sites on Mcl-1. Members classes were merged together produce lead...
Significance Ras is one of the most highly validated targets in cancer; however, discovery potent inhibitors has been difficult to achieve. We report small molecules that bind a pocket on Ras:Son Sevenless:Ras complex and alter activity biochemical cell-based experiments. High-resolution cocrystal structures define protein–ligand interactions, lead compounds provide starting point for signaling.
Sunitinib is a multitargeted tyrosine kinase inhibitor associated with idiosyncratic hepatotoxicity. The mechanisms of this toxicity are unknown. We hypothesized that sunitinib undergoes metabolic activation to form chemically reactive, potentially toxic metabolites which may contribute development sunitinib-induced purpose study was define the role cytochrome P450 (P450) enzymes in bioactivation. Metabolic incubations were performed using individual recombinant P450s, human liver microsomal...
Deregulated RAS activity, often the result of mutation, is implicated in approximately 30% all human cancers. Despite this statistic, no clinically successful treatment for RAS-driven tumors has yet been developed. One approach modulating activity to target and affect proteins that interact with RAS, such as guanine nucleotide exchange factor (GEF) son sevenless homologue 1 (SOS1). Here, we report on structure–activity relationships (SAR) an indole series compounds. Using structure-based...
Synthetic efforts toward the cytotoxic peptides lucentamycins A−D are described that resulted in total synthesis and biological evaluation of 8-epi-lucentamycin A 15 steps with 2.2% overall yield. The key epi-nonproteogenic 3-methyl-4-ethylideneproline was synthesized via a titanium-mediated cycloisomerization reaction.
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTA New Catalytic Cu(II)/Sparteine Oxidant System for β,β-Phenolic Couplings of Styrenyl Phenols: Synthesis Carpanone and Unnatural AnalogsR. Nathan Daniels, Olugbeminiyi O. Fadeyi, Craig W. LindsleyView Author Information Departments Chemistry Pharmacology, Institute Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232[email protected]Cite this: Org. Lett. 2008, 10, 18, 4097–4100Publication Date (Web):August 27, 2008Publication History...
The first total synthesis of Ciliatamides A−C was completed, leading to a revision the reported stereochemistry from (S,S) (R,R) enantiomers. Due expedited route, library over 50 unnatural ciliatamide analogs also prepared.
A new, non-SSRI mechanism of action for Prozac™. Unquestionably, Prozac™ was a landmark drug that redefined the treatment depression, anxiety disorders, premenstrual syndrome and post-traumatic stress disorder as well ushering in wave new therapies targeting specific serotonin (5-HT) reuptake inhibition (SSRI) [1]. In recent manuscript (Psychopharmacology 2006, 186, 362-372), Pinna co-workers report fluoxetine its N-desmethyl congener norfluoxetine stereospecifically selectively increase...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract Purpose: Sunitinib is a multi-targeted tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. However, clinical use sunitinib associated with potentially fatal idiosyncratic liver injury. The mechanisms this toxicity are unknown. We hypothesized that undergoes metabolic activation to form chemically reactive, toxic metabolites, which may contribute development sunitinib-induced purpose...
Abstract Aberrant activation of Ras, by mutation or constitutively active upstream kinases, occurs in nearly 30% all human cancers, rendering Ras one the most validated targets cancer drug discovery. Historically, direct inhibition with small molecules has proven extremely difficult. Here we report discovery compounds that bind to a unique pocket on Ras:SOS:Ras complex, which increase rate SOScat-catalyzed nucleotide exchange vitro and modulate signaling pathways cells. X-ray crystallography...
Abstract Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active receptor tyrosine kinases (RTKs) results in deregulation cellular signals governing growth and survival cancer. The guanine nucleotide exchange factor Son Sevenless (SOS) catalyzes rate-limiting step exchanging GDP for GTP. SOS is therefore a key control point propagation RTK signaling. Here we report discovery molecules that bind to unique pocket on Ras:SOS:Ras complex, increase...