title: Development of PAC-14028, a novel transient receptor potential vanilloid type 1 (TRPV1) channel antagonist as a new drug for refractory skin diseases.
abstract: The transient receptor potential vanilloid 1 (TRPV1) is a member of nonselective cation channels and has been implicated in the progression of neurogenic inflammation and nociception. Through the synthesis of over 2,000 new compounds, a novel non-vanilloid TRPV1 antagonist PAC-14028 was discovered. As well as ideal physicochemical and pharmacokinetic properties, PAC-14028 showed meaningful efficacies against diverse disease models that include visceral pain, inflammatory bowel disease, and inflammatory pain. Of note, PAC-14028 effectively attenuates atopic dermatitis and pruritus without significant adverse effects, which is a substantial benefit over conventional pharmacotherapy. This report introduces the potential of a novel TRPV1 antagonist PAC-14028 as a new drug for atopic dermatitis and pruritus.
authors.affiliation: Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Korea. kimlim@amorepacific.com
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
mesh_terms: D000178:Acrylamides / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000982:Antipruritics / Q000009:adverse effects / Q000627:therapeutic use*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D011537:Pruritus / Q000188:drug therapy* / Q000378:metabolism; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000178:Acrylamides; D000893:Anti-Inflammatory Agents; D000982:Antipruritics; D015507:Drugs, Investigational; C559614:N-(1-(3,5-difluoro-4-methanesulfonylaminophenyl)ethyl)-3-(2-propyl-6-trifluoromethylpyridine-3-yl)acrylamide; D011725:Pyridines; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human