TABLE 2

Affinity values and dissociation characteristics of ZM241385 at the wild-type (WT) and mutant adenosine A2A receptors

MutantpKiDifference from WT koffaFold over WT RTb
M pKi unitsmin−1koffmin
WT7.83 ± 0.040.000.0119 ± 0.00061.0084 ± 2
I662.63A7.84 ± 0.040.010.0071 ± 0.00020.60141 ± 2
S672.64A7.93 ± 0.040.100.0077 ± 0.00040.64130 ± 4
T682.65A7.85 ± 0.040.020.0113 ± 0.00040.9589 ± 2
Q148ECL2A7.78 ± 0.05−0.050.0148 ± 0.00091.2468 ± 2
K153ECL2A7.91 ± 0.050.080.0094 ± 0.00050.79106 ± 3
S156ECL2A7.98 ± 0.060.150.0128 ± 0.00071.0878 ± 3
Q157ECL2A8.03 ± 0.06*0.200.0112 ± 0.00060.9489 ± 3
E169ECL2AN/AN/AN/AN/AN/A
E169ECL2Q7.46 ± 0.04****−0.370.7329 ± 0.0616****61.61.4 ± 0.1
T2566.58A7.43 ± 0.05****−0.400.1994 ± 0.0120****16.85.0 ± 0.2
H2647.29A7.69 ± 0.05−0.140.2235 ± 0.0096****18.84.5 ± 0.1
L2677.32A7.78 ± 0.04−0.050.0051 ± 0.00020.43196 ± 5
Y2717.36AN/AN/AN/AN/AN/A
  • Data are represented as mean ± S.E.M. of three separate experiments each preformed in duplicate. Significantly different from wild-type with *P < 0.05, ****P < 0.0001 (one-way analysis of variance with Dunnett’s test).

  • a Obtained by fitting data into the model of one-phase exponential decay.

  • b Residence time (RT ) = 1/koff (koff from one-phase exponential decay); N/A, not available.