Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin

Richard D. Carpenter, Mirela Andrei, Edmond Y Lau, Felice C Lightstone, Ruiwu Liu, Kit Lam, Mark J. Kurth

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5863-5867
Number of pages5
JournalJournal of Medicinal Chemistry
Volume50
Issue number23
DOIs
StatePublished - Nov 15 2007

Fingerprint

Pharmacokinetics
Integrins
Solubility
Urea
Lymphoma
Peptidomimetics
Water
Cell Surface Receptors
Inhibitory Concentration 50
benzimidazole

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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; Kurth, Mark J.

In: Journal of Medicinal Chemistry, Vol. 50, No. 23, 15.11.2007, p. 5863-5867.

Research output: Contribution to journalArticle

Carpenter, Richard D. ; Andrei, Mirela ; Lau, Edmond Y ; Lightstone, Felice C ; Liu, Ruiwu ; Lam, Kit ; Kurth, Mark J. / Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 23. pp. 5863-5867.
@article{0f32fcbe8f7244d991ea08ee583d9e35,
title = "Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin",
abstract = "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.",
author = "Carpenter, {Richard D.} and Mirela Andrei and Lau, {Edmond Y} and Lightstone, {Felice C} and Ruiwu Liu and Kit Lam and Kurth, {Mark J.}",
year = "2007",
month = "11",
day = "15",
doi = "10.1021/jm070790o",
language = "English (US)",
volume = "50",
pages = "5863--5867",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

TY - JOUR

T1 - Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin

AU - Carpenter, Richard D.

AU - Andrei, Mirela

AU - Lau, Edmond Y

AU - Lightstone, Felice C

AU - Liu, Ruiwu

AU - Lam, Kit

AU - Kurth, Mark J.

PY - 2007/11/15

Y1 - 2007/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=36148929378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36148929378&partnerID=8YFLogxK

U2 - 10.1021/jm070790o

DO - 10.1021/jm070790o

M3 - Article

C2 - 17948981

AN - SCOPUS:36148929378

VL - 50

SP - 5863

EP - 5867

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -