A5078255099- Neuropeptides and Animal Physiology
- Pain Mechanisms and Treatments
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Protein Kinase Regulation and GTPase Signaling
- Pharmacological Receptor Mechanisms and Effects
- Shoulder Injury and Treatment
- Orthopedic Surgery and Rehabilitation
- Melanoma and MAPK Pathways
- Orthopedic Infections and Treatments
- Shoulder and Clavicle Injuries
- Botulinum Toxin and Related Neurological Disorders
- Total Knee Arthroplasty Outcomes
- Nicotinic Acetylcholine Receptors Study
- Adenosine and Purinergic Signaling
- Pelvic and Acetabular Injuries
- Orthopaedic implants and arthroplasty
- Spinal Fractures and Fixation Techniques
- Asthma and respiratory diseases
- Hypothalamic control of reproductive hormones
- Biochemical and Molecular Research
- PI3K/AKT/mTOR signaling in cancer
- Allergic Rhinitis and Sensitization
- Peptidase Inhibition and Analysis
SiteOne Therapeutics (United States)
2019-2024
University Hospitals of Cleveland
2019
Case Western Reserve University
2019
The University of Texas Southwestern Medical Center
2013-2018
University of Southern Denmark
2017
University of California, Davis
1997-2016
Southwestern Medical Center
2014-2015
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010-2014
University of Oklahoma
2014
University of California Davis Medical Center
2006-2013
KRAS mutations are the most common genetic abnormalities in cancer, but distribution of specific across cancers and differential responses patients with therapeutic clinical trials suggest that different have unique biochemical behaviors. To further explain these high-level differences to explore potential strategies for isoforms, we characterized mutants biochemically substrate binding kinetics, intrinsic GTPase-activating protein (GAP)-stimulated GTPase activities, interactions RAS...
PD134308 and PD135158 are potent selective antagonists at the cholecystokinin type B (CCK-B) receptors with IC50 values of 1.6 nM 3.5 nM, respectively, in radioligand binding assay Ke 7.82 12.9 their blocking action on CCK responses rat lateral hypothalamic slice. produced anxiolytic effects mouse black/white box test after either subcutaneous or oral administration. There was no evidence development tolerance to mice treated twice daily for 7 days, nor there any sign withdrawal anxiogenesis...
Small neurons of the dorsal root ganglia (DRG) are known to play an important role in nociceptive mechanisms. These express two types sodium current, which differ their inactivation kinetics and sensitivity tetrodotoxin. Here, we report cloning α-subunit a novel, voltage-gated channel (PN3) from rat DRG. Functional expression Xenopus oocytes showed that PN3 is with depolarized activation potential, slow kinetics, resistance high concentrations In situ hybridization DRG indicated expressed...
Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to peripheral nerves. Such has been hypothesized be the result of an aberrant expression and function sodium channels at site injury. Here, we show intrathecal administration specific antisense oligodeoxynucleotides (ODN) tetrodotoxin (TTX)-resistant channel, NaV1.8, resulted in time-dependent uptake ODN by dorsal root ganglion (DRG) neurons, selective "knock-down" reduction slow-inactivating, TTX-resistant...
Abstract We report the synthesis of a GDP analogue, SML‐8‐73‐1, and prodrug derivative, SML‐10‐70‐1, which are selective, direct‐acting covalent inhibitors K‐Ras G12C mutant relative to wild‐type Ras. Biochemical biophysical measurements suggest that modification with SML‐8‐73‐1 renders protein in an inactive state. These first‐in‐class demonstrate irreversible targeting guanine‐nucleotide binding site is potentially viable therapeutic strategy for inhibition Ras signaling.
Significance SML-8-73-1 (SML) is the first example, to our knowledge, of a GTP-competitive inhibitor V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras). A high-resolution structure K-Ras G12C bound SML shows in an inactive conformation. In situ proteomic-based chemical profiling demonstrates that highly selective for over other small GTPases. novel chemosensor-based assay allows measurement covalent reaction rates between and enables characterization this context millimolar...
The novel sodium channel PN3/α-SNS, which was cloned from a rat dorsal root ganglion (DRG) cDNA library, is expressed predominantly in small sensory neurons and may contribute to the tetrodotoxin-resistant (TTX R ) current that believed be associated with central sensitization chronic neuropathic pain states. To assess further role of PN3, we have used electrophysiological, situ hybridization immunohistochemical methods monitor changes TTX distribution PN3 normal peripheral nerve-injured...
1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation acute nociception, motor behaviour and body temperature, has been investigated by determining activity alpha2AR selective agonist dexmedetomidine (Dex) mice devoid individual through either a point (alpha2A) or null (alpha2B/alpha2C) mutation ('knock-out'). 2. In rodent model thermal mouse tail immersion test, Dex, wild type (WT) control animals, produced dose-dependent increase threshold for withdrawal from 52 degrees C...
Dorsal root ganglion neurons express a wide repertoire of sodium channels with different properties. Here, we report the cloning from rat, dorsal ganglia (DRG), cellular expression, and functional analysis novel tetrodotoxin-sensitive peripheral channel (PN), PN1. PN1 mRNA is expressed in many tissues. Within rat DRG, both PN1-like immunoreactivity are present small large neurons. The abundance mRNAs DRG rBI > ≥ PN3 >>> rBIII by quantitative reverse transcription-polymerase chain reaction...
P2X3 purinoceptor cellular distribution was studied in rat sensory neurons naive animals and following peripheral nerve injury using immunohistochemical methods. Specific antiserum raised rabbits characterized by Western blot, absorption assays labeling of recombinant receptors. In animals, immunoreactivity present predominantly a subpopulation small-diameter dorsal root ganglia. the spinal cord, observed superficial laminae horn. Following chronic constriction to sciatic nerve, number...
The adenosine A<sub>2A</sub> receptor has been implicated in the underlying biology of various neurological and psychiatric disorders, including Parkinson9s disease (PD) depression. Preladenant SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7<i>H</i>-pyrazolo[4,3-<i>e</i>][1,2,4]triazolo[1,5-<i>c</i>]pyrimidin-5-amine] are potent competitive antagonists human (<i>K</i><sub>i</sub> = 1.1 0.6 nM, respectively) have >1000-fold selectivity over all other receptors,...
MR imaging of clinically suspected scaphoid fractures.J C Hunter, E M Escobedo, A J Wilson, D P Hanel, G Zink-Brody and F MannAudio Available | Share
CI‐977 is a new, nonpeptide κ‐opioid compound that has been synthesized and its pharmacological properties determined in series of vitro vivo rodent models. In radioligand binding studies, with guinea‐pig forebrain homogenates, bound high affinity to [ 3 H]‐U69593‐labelled κ‐sites ( K i = 0.11 n m ) but low H]‐[ d ‐Ala 2 , MePhe 4 Glyol 5 ] enkephalin (DAMGO) labelled μ‐sites 99n ‐Pen 2,5 ]enkephalin (DPDPE) δ‐sites 1.04 μ ). also negligible H]‐(+)‐3‐(1‐propyl‐3‐piperidinyl)phenol (3‐PPP)...
A number of novel amidine containing heterocycles were designed to reproduce the unique interaction pattern, revealed by X-ray crystallography, between BACE-1 catalytic diad and a weak NMR screening hit (3), with special attention paid maintaining appropriate basicity limiting H-bonding donors these scaffolds. The iminohydantoin cores (10 23) examined first found interact in one two binding modes (A B), each core flipped 180° relation other. structural motif within forms bidentate different...