Highly potent, water soluble benzimidazole antagonist for activated alpha 4 beta 1 integrin.
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.
Carpenter
Richard D
RD
Department of Chemistry, University of California, Davis, Davis, CA 95616, USA.
Andrei
Mirela
M
Lau
Edmond Y
EY
Lightstone
Felice C
FC
Liu
Ruiwu
R
Lam
Kit S
KS
Kurth
Mark J
MJ
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
D001562:Benzimidazoles; D039041:Integrin alpha4beta1