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. Author manuscript; available in PMC: 2019 May 10.
Published in final edited form as: J Med Chem. 2018 Apr 20;61(9):4067–4086. doi: 10.1021/acs.jmedchem.8b00091

Table 1.

Kinetic Parameters

KPC-2 Ki app (μM) k2/K (M−1 s−1) koff (s−1) half-life (min) Kd (nM) kcat/kinact
3 0.32 ± 0.03 2.4 ± 0.9 × 105 4.5 ± 0.5 × 10−4 26 ± 3 1.9 ± 0.2 1
2 4.5 ± 0.5 9.4 ± 0.6 × 103 4.0 ± 0.4 × 10−4 29 ± 3 43 ± 5 1
1 7.8 ± 0.8 8.8 ± 0.9 × 103 3.5 ± 0.5 × 10−4 33 ± 5 40 ± 7 1
avibactam 0.9 ± 0.1 1.3 × 104a 1.4 × 10−4a 82a 11a 1
relebactam 2.2 ± 0.3 2.8 ± 0.3 × 104 2.5 ± 0.5 × 10−4 46 ± 9 9 ± 2 1
ADC-7 Ki app (μM) k2/K (M−1 s−1) koff (s−1) half-life (min) Kd (nM) kcat/kinact
3 8.0 ± 0.8 1.9 ± 0.2 × 104 1.0 ± 0.1 × 10−3 12 ± 2 53 ± 7 6
2 2.3 ± 0.3 3.5 ± 0.4 × 104 1.1 ± 0.1 × 10−3 11 ± 1 32 ± 3 4
1 3.7 ± 0.4 3.2 ± 0.3 × 104 9.0 ± 0.1 × 10−4 13 ± 1 29 ± 3 4
avibactam 19 ± 2 3.9 ± 0.4 × 103 3.5 ± 0.5 × 10−4 33 ± 5 90 ± 9 4
relebactam 12.6 ± 2 7.8 ± 0.8 × 103 3.0 ± 0.3 × 10−4 39 ± 4 39 ± 4 2
PDC-3 Ki app (μM) k2/K (M−1 s−1) koff (s−1) half-life (min) Kd (nM) kcat/kinact
3 3.8 ± 0.4 2.3 ± 0.2 × 104 2.8 ± 0.3 × 10−3 4.1 ± 0.4 124 ± 18 5
2 0.14 ± 0.01 4.8 ± 0.7 × 105 3.5 ± 0.4 × 10−3 3.3 ± 0.4 7.3 ± 1.4 1
1 0.13 ± 0.02 6.3 ± 0.6 × 105 4.0 ± 0.4 × 10−3 2.9 ± 0.3 6.3 ± 0.9 1
avibactam 2.5 ± 0.3a 2.9 × 104a 8 × 10−4a 14.4a 27.6a 1
relebactam 3.2 ± 0.3 4.6 ± 0.5 × 104 9.0 ± 0.1 × 10−4 12.8 ± 1.4 20 ± 3 1
OXA-23 Ki app (μM) k2/K (M−1 s−1) koff (s−1) half-life (min) Kd (nM) kcat/kinact
3 8±1 1.7 ± 0.2 × 104 5.0 ± 0.5 × 10−4 23 ± 2 29 ± 4 1
2 >100 ND ND ND ND ND
1 >100 ND ND ND ND ND
avibactam >100 3 × 102a 8.0 × 10−6a 1,436a 27a ND
relebactam >100 ND ND ND ND ND
OXA-24/40 Ki app (μM) k2/K (M−1 s−1) koff (s−1) half-life (min) Kd (nM) kcat/kinact
3 5.0 ± 0.5 9.6 ± 1.0 × 103 4.0 ± 0.4 × 10−4 29 ± 3 42 ± 6 2
2 >100 ND ND ND ND ND
1 >100 ND ND ND ND ND
avibactam >100 5.2 × 101a 6.3 × 10−6a 1,823a 121a ND
relebactam >100 ND ND ND ND ND
OXA-48 Ki app (μM) k2/K (M−1 s−1) koff (s−1) half-life (min) Kd (nM) kcat/kinact
3 0.29 ± 0.03 6.4 ± 0.6 × 105 9.0 ± 0.1 × 10−4 13 ± 1 1.4 ± 0.2 2
2 >100 ND ND ND ND ND
1 >100 ND ND ND ND ND
avibactam 30 ± 3 1.4 × 103a 1.2 ± × 10−5a 1,000a 9a 1
relebactam >100 ND ND ND ND ND
a

Previously published data.4,5 ND: if Ki app values were >100 μM, then further kinetic analyses were not determined.