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Overview
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Background
BIO 1211 is a selective and high affinity inhibitor of α4β1 with IC50 value of 0.004uM [1].The leukocyte integrin α4β1 mediates leukocyte recruitment, activation, apoptosis inhibition and mediator release, it plays an important role in inflammatory responses [1].BIO-1211 was about 200-fold selective for the activated form of α4β1 and it stimulated expression of ligand-induced epitopes on the integrin β1 subunit, consistent with occupancy of the receptor’s ligand-binding site [1]. In Jurkat cells, KD values for BIO1211 binding ranged from 20–40 nM in the nonactivated state of the integrin to 100 pM in the activated state. Different KD values were controlled exclusively by differences in the dissociation rates of the integrin-BIO1211 complex [2].Treatment allergic sheep with a 3-mg nebulized dose BIO-1211, BIO-1211 prevented nonspecific airway hyperresponsiveness to carbachol and inhibited early and late airway responses following antigen challenge [1].
[1]. Lin Kc, Ateeq HS, Hsiung SH, et al. Selective, tight-binding inhibitors of integrin α4β1 that inhibit allergic airway responses. J Med Chem, 1999, 42(5): 920-934.
[2]. Chen LL, Whitty A, Lobb RR, et al. Multiple activation sites of integrin α4β1 detected through their different affinities for a small molecule ligand. J Biol Chem, 1999, 274(19): 13167-13175.
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