22676-74-0Relevant academic research and scientific papers
Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin
Carpenter, Richard D.,Andrei, Mirela,Lau, Edmond Y.,Lightstone, Felice C.,Liu, Ruiwu,Lam, Kit S.,Kurth, Mark J.
, p. 5863 - 5867 (2007)
The cell surface receptor α4β1 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.
Selectively targeting T- and B-cell lymphomas: A benzothiazole antagonist of α4β1integrin
Carpenter, Richard D.,Andrei, Mirela,Aina, Olulanu H.,Lau, Edmond Y.,Lightstone, Felice C.,Liu, Ruiwu,Lam, Kit S.,Kurth, Mark J.
experimental part, p. 14 - 19 (2009/11/30)
Current cancer chemotherapeutic agents clinically deployed today are designed to be indiscriminately cytotoxic, however, achieving selective targeting of cancer malignancies would allow for improved diagnostic and chemotherapeutic tools. Integrin α4β1, a heterodimeric cell surface receptor, is believed to have a low- affinity conformation in resting normal lymphocytes and an activated high-affinity conformation in cancerous cells, specifically T- and B-cell lymphomas. This highly attractive yet poorly understood receptor has been selectively targeted with the bisaryl urea peptidomimetic antagonist i. However, concerns regarding its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzothiazole moiety, resulting in an analogue with improved physicochemical properties, solubility, and kidney:tumor ratio while maintaining potency (6;IC50 = 53 pM). The results presented herein utilized heterocyclic and solid-phase chemistry, cell adhesion assay, and in vivo optical imaging using the cyanine dye Cy5.5 conjugate.
HETEROCYCLIC LIGANDS FOR INTEGRIN IMAGING AND THERAPY
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Page/Page column 38, (2010/11/30)
The present invention provides α 4?1 integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.
