FIGURE 1.
BTT-3033 and BTT-3034 are potent inhibitors of α2β1 integrin. Chemical structures of BTT-3033 (A) and BTT-3034 (B) are shown. The inhibitory effects and selectivity of BTT-3033 (C) and BTT-3034 (D) were tested by measuring CHO-α2β1 (□) and CHO -α1β1 (Δ) cell adhesion to collagen I and collagen IV, respectively. Cells were allowed to attach to collagen matrices for 2 h, and adherent cells were detected with the WST-1 reagent. BTT-3033 and BTT-3034 inhibited the adhesion of CHO-α2wt cells on collagen I with EC50 values of 130 and 160 nm, respectively, and corresponding Emax values of 97 and 86%. The selectivity versus α1β1 integrin was determined by comparing EC50 values in CHO-α1wt/collagen IV assay to those in CHO-α2wt/collagen I assays. The selectivity of BTT-3033 for α2β1 integrin (8-fold) was greater than that of BTT-3034 (2-fold).