title: Multi-inhibitor prodrug constructs for simultaneous delivery of anti-inflammatory agents to mustard-induced skin injury.
abstract: 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 development domain over the last 8 years.
authors: Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania.
authors: Carl J
authors: CJ
authors: Lacey
authors: Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, New Jersey.
authors: Irene
authors: I
authors: Wohlman
authors: Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania.
authors: Christophe
authors: C
authors: Guillon
authors: Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania.
authors: Jaya
authors: J
authors: Saxena
authors: Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania.
authors: Cynthia
authors: C
authors: Fianu-Velgus
authors: Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania.
authors: Erik
authors: E
authors: Aponte
authors: Department of Chemistry, Muhlenberg College, Allentown, Pennsylvania.
authors: Sherri C
authors: SC
authors: Young
authors: Department of Environmental Health Science, New York Medical College, Valhalla, New York.
authors: Diane E
authors: DE
authors: Heck
authors: Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, New Jersey.
authors: Laurie B
authors: LB
authors: Joseph
authors: Department of Environmental and Occupational Health, Rutgers University School of Public Health, Piscataway, New Jersey.
authors: Jeffrey D
authors: JD
authors: Laskin
authors: Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania. ndh0@lehigh.edu.
authors: Ned D
authors: ND
authors: Heindel
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000378:metabolism / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D009151:Mustard Gas / Q000378:metabolism / Q000633:toxicity*; D011355:Prodrugs / Q000008:administration & dosage* / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D016861:Cyclooxygenase Inhibitors; D011355:Prodrugs; D009151:Mustard Gas
keywords: bifunctionals; chloroethylethylsulfide; inflammation; phorbol ester; skin; sulfur mustard; vesicants