title: Highly potent, water soluble benzimidazole antagonist for activated alpha 4 beta 1 integrin.
abstract: The cell surface receptor alpha 4 beta 1 integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety, resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC50 = 305 pM]. With exceptional solubility, this finding has the potential for improving PK to help diagnose and treat lymphomas.
authors.affiliation: Department of Chemistry, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carpenter
authors.forename: Mirela
authors.initials: M
authors.lastname: Andrei
authors.forename: Edmond Y
authors.initials: EY
authors.lastname: Lau
authors.forename: Felice C
authors.initials: FC
authors.lastname: Lightstone
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Liu
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kurth
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D039041:Integrin alpha4beta1