Carl Jeffrey Lacey
Lehigh University
ProdrugPharmacokineticsInternal medicineDownregulation and upregulationEndocrinologyPathologyBlood proteinsReceptorEnzymeChemistryIn vitroImmunologyIn vivoMechanism of actionVasopressinAntagonistInflammationDoxycyclineDermisCorneal neovascularizationReceptor antagonistSRX246Blood–brain barrierNitrogen mustardAnti-inflammatoryWound healingSulfur mustardAntidiuretic Hormone Receptor AntagonistsCell DegranulationCorneal DiseasesNitrogen Mustard CompoundSpect imagingAntibacterial agentDegranulationNecrosisPlasma protein bindingDrug developmentMedicineMolecular pathologyBiologyPharmacology
Publications 5
#1Laurie B. Joseph (RU: Rutgers University)H-Index: 12
#2Gabriella M. Composto (RU: Rutgers University)H-Index: 5
Last. Diane E. Heck (NYMC: New York Medical College)H-Index: 4
view all 13 authors...
Abstract Sulfur mustard (SM, bis(2-chloroethyl sulfide) is a potent vesicating agent known to cause skin inflammation, necrosis and blistering. Evidence suggests that inflammatory cells and mediators that they generate are important in the pathogenic responses to SM. In the present studies we investigated the role of mast cells in SM-induced skin injury using a murine vapor cup exposure model. Mast cells, identified by toluidine blue staining, were localized in the dermis, adjacent to dermal app...
9 CitationsSource
#1Carl Jeffrey Lacey (Lehigh University)H-Index: 4
#2Irene M. Wohlman (RU: Rutgers University)H-Index: 3
Last. Ned D. Heindel (Lehigh University)H-Index: 20
view all 11 authors...
The molecular pathology of sulfur mustard injury is complex, with at least nine inflammation-related enzymes and receptors upregulated in the zone of the insult. A new approach wherein inhibitors of these targets have been linked by hydrolyzable bonds, either one to one or via separate preattachment to a carrier molecule, has been shown to significantly enhance the therapeutic response compared with the individual agents. This article reviews the published work of the authors in this drug develo...
4 CitationsSource
#1Karine Fabio (Lehigh University)H-Index: 6
#2Christophe Guillon (Lehigh University)H-Index: 8
Last. Neal G. Simon (Lehigh University)H-Index: 21
view all 8 authors...
ABSTRACT SRX246 is a potent, highly selective, orally bioavailable vasopressin 1a receptor antagonist that represents a novel mechanism of action for the treatment of mood disorders. The compound previously showed efficacy in animal models of mood disorders and excellent safety and tolerability in healthy volunteers in phase I clinical trials. In this study, SRX246 was further characterized in rats and dogs. In vitro determinations of permeability, protein binding, hepatocyte metabolism, and cyt...
23 CitationsSource
#1Karine Fabio (Lehigh University)H-Index: 6
#2Christophe Guillon (Lehigh University)H-Index: 8
Last. Neal G. Simon (Lehigh University)H-Index: 21
view all 10 authors...
SRX246 is a potent, highly selective human vasopressin V1a antagonist that crosses the blood–brain barrier in rats. CNS penetration makes SRX246 an ideal candidate for potential radiolabeling and use in visualization and characterization of the role of the V1a receptor in multiple stress-related disorders. Before radiolabeling studies, cold reference analogs of SRX246 were prepared. This study describes the synthesis and in vitro screening for human V1a receptor binding and permeability of fluor...
18 CitationsSource
#1Marion K. Gordon (RU: Rutgers University)H-Index: 21
#2Andrea S. DeSantis (RU: Rutgers University)H-Index: 2
Last. Patrick J. Sinko (RU: Rutgers University)H-Index: 62
view all 14 authors...
Abstract Purpose: The goals of this study were (1) to compare the injury at the basement membrane zone (BMZ) of rabbit corneal organ cultures exposed to half mustard (2 chloroethyl ethyl sulfide, CEES) and nitrogen mustard with that of in vivo rabbit eyes exposed to sulfur mustard (SM); (2) to test the efficacy of 4 tetracycline derivatives in attenuating vesicant-induced BMZ disruption in the 24-h period postexposure; and (3) to use the most effective tetracycline derivative to compare the impr...
44 CitationsSource