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

doi:10.1021/jm070790o

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 journal › Article › peer-review

27 Scopus citations

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 language	English (US)
Pages (from-to)	5863-5867
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	50
Issue number	23
DOIs	https://doi.org/10.1021/jm070790o
State	Published - Nov 15 2007

ASJC Scopus subject areas

Organic Chemistry

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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.",

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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.

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