FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4312933391> ?p ?o ?g. }

• W4312933391 endingPage "379" @default.
• W4312933391 startingPage "367" @default.
• W4312933391 abstract "Abstract: Drug therapy for the major inflammatory skin diseases, which include atopic dermatitis, psoriasis and allergic contact dermatitis, is often inadequate due to poor efficacy, toxicity, or both. Much research has focused on the macrolactam T cell inhibitors as a promising new class of agents for immunotherapy, and medicinal chemistry efforts to design novel ascomycin analogs have produced clinically promising agents. A synthetic program to modify the ascomycin nucleus to alter its physicochemical properties and promote systemic clearance is described. A biologic screening strategy to identify analogs with reduced systemic activity and rapid phannacokinetic elimination led to identification of the clinical candidate, ABT-281. A swine contact hypersensitivity model was used as a stringent indicator of skin penetration as human doses of topical corticosteroids produced inhibition only in the 50% range and ED50 values were 100-fold less potent than in rat. Also, cyclosporine was confirmed to be topically inactive in swine, as seen in human. ABT-281 had topical potency equal to tacrolimus (FKS06) despit_e a severalfold lower potency for inhibiting swine T cells in vitro, consistent-with superior skin penetration. ABT-281 was found to have a shorter duration of action after i.v. dosing in monkeys using an ex vivo whole blood IL-2 production assay. Systemic potency was reduced by 30- fold or more in rat popliteal lymph node hyperplasia and contact hypersensitivity assays. Following i.v. or i.p. administration in the swine contact hypersensitivity model, ABT-281 was 19- and 61-fold less potent, respectively, than FK506. Pharmacokinetic studies showed that ABT-281 had a shorter half life and higher rate of clearance than FKS06 in all three species. The potent topical activity and reduced sytemic exposure of ABT- 281 may thus provide both efficacy and a greater margin of safety for topical therapy of skin diseases." @default.
• W4312933391 created "2023-01-05" @default.
• W4312933391 creator A5006562450 @default.
• W4312933391 creator A5017032095 @default.
• W4312933391 creator A5019347322 @default.
• W4312933391 creator A5021646889 @default.
• W4312933391 creator A5025931880 @default.
• W4312933391 creator A5026712754 @default.
• W4312933391 creator A5026852803 @default.
• W4312933391 creator A5033879713 @default.
• W4312933391 creator A5040158129 @default.
• W4312933391 creator A5041334007 @default.
• W4312933391 creator A5042224478 @default.
• W4312933391 creator A5043422189 @default.
• W4312933391 creator A5043521186 @default.
• W4312933391 creator A5043866994 @default.
• W4312933391 creator A5059158159 @default.
• W4312933391 creator A5060641809 @default.
• W4312933391 creator A5062122842 @default.
• W4312933391 creator A5067339265 @default.
• W4312933391 creator A5073014007 @default.
• W4312933391 creator A5075287321 @default.
• W4312933391 creator A5076677575 @default.
• W4312933391 creator A5077629440 @default.
• W4312933391 creator A5080087435 @default.
• W4312933391 creator A5081639279 @default.
• W4312933391 creator A5084180043 @default.
• W4312933391 creator A5084977296 @default.
• W4312933391 creator A5086640568 @default.
• W4312933391 creator A5089793941 @default.
• W4312933391 date "1998-10-01" @default.
• W4312933391 modified "2023-09-27" @default.
• W4312933391 title "Discovery of Ascomycin Analogs with Potent Topical but Weak Systemic Activity for Treatment of Inflammatory Skin Diseases" @default.
• W4312933391 doi "https://doi.org/10.2174/138161280405221010155826" @default.
• W4312933391 hasPublicationYear "1998" @default.
• W4312933391 type Work @default.
• W4312933391 citedByCount "9" @default.
• W4312933391 countsByYear W43129333912017 @default.
• W4312933391 countsByYear W43129333912021 @default.
• W4312933391 crossrefType "journal-article" @default.
• W4312933391 hasAuthorship W4312933391A5006562450 @default.
• W4312933391 hasAuthorship W4312933391A5017032095 @default.
• W4312933391 hasAuthorship W4312933391A5019347322 @default.
• W4312933391 hasAuthorship W4312933391A5021646889 @default.
• W4312933391 hasAuthorship W4312933391A5025931880 @default.
• W4312933391 hasAuthorship W4312933391A5026712754 @default.
• W4312933391 hasAuthorship W4312933391A5026852803 @default.
• W4312933391 hasAuthorship W4312933391A5033879713 @default.
• W4312933391 hasAuthorship W4312933391A5040158129 @default.
• W4312933391 hasAuthorship W4312933391A5041334007 @default.
• W4312933391 hasAuthorship W4312933391A5042224478 @default.
• W4312933391 hasAuthorship W4312933391A5043422189 @default.
• W4312933391 hasAuthorship W4312933391A5043521186 @default.
• W4312933391 hasAuthorship W4312933391A5043866994 @default.
• W4312933391 hasAuthorship W4312933391A5059158159 @default.
• W4312933391 hasAuthorship W4312933391A5060641809 @default.
• W4312933391 hasAuthorship W4312933391A5062122842 @default.
• W4312933391 hasAuthorship W4312933391A5067339265 @default.
• W4312933391 hasAuthorship W4312933391A5073014007 @default.
• W4312933391 hasAuthorship W4312933391A5075287321 @default.
• W4312933391 hasAuthorship W4312933391A5076677575 @default.
• W4312933391 hasAuthorship W4312933391A5077629440 @default.
• W4312933391 hasAuthorship W4312933391A5080087435 @default.
• W4312933391 hasAuthorship W4312933391A5081639279 @default.
• W4312933391 hasAuthorship W4312933391A5084180043 @default.
• W4312933391 hasAuthorship W4312933391A5084977296 @default.
• W4312933391 hasAuthorship W4312933391A5086640568 @default.
• W4312933391 hasAuthorship W4312933391A5089793941 @default.
• W4312933391 hasConcept C112705442 @default.
• W4312933391 hasConcept C150903083 @default.
• W4312933391 hasConcept C185592680 @default.
• W4312933391 hasConcept C202751555 @default.
• W4312933391 hasConcept C203014093 @default.
• W4312933391 hasConcept C207001950 @default.
• W4312933391 hasConcept C207480886 @default.
• W4312933391 hasConcept C25938499 @default.
• W4312933391 hasConcept C26291073 @default.
• W4312933391 hasConcept C2776056826 @default.
• W4312933391 hasConcept C2778091633 @default.
• W4312933391 hasConcept C2778329239 @default.
• W4312933391 hasConcept C2780035454 @default.
• W4312933391 hasConcept C2780564577 @default.
• W4312933391 hasConcept C55493867 @default.
• W4312933391 hasConcept C57992300 @default.
• W4312933391 hasConcept C71924100 @default.
• W4312933391 hasConcept C86803240 @default.
• W4312933391 hasConcept C98274493 @default.
• W4312933391 hasConceptScore W4312933391C112705442 @default.
• W4312933391 hasConceptScore W4312933391C150903083 @default.
• W4312933391 hasConceptScore W4312933391C185592680 @default.
• W4312933391 hasConceptScore W4312933391C202751555 @default.
• W4312933391 hasConceptScore W4312933391C203014093 @default.
• W4312933391 hasConceptScore W4312933391C207001950 @default.
• W4312933391 hasConceptScore W4312933391C207480886 @default.
• W4312933391 hasConceptScore W4312933391C25938499 @default.
• W4312933391 hasConceptScore W4312933391C26291073 @default.
• W4312933391 hasConceptScore W4312933391C2776056826 @default.
• W4312933391 hasConceptScore W4312933391C2778091633 @default.

• next