Table 1.
The kinetics of VX- and sarin-detoxification, and sarin-BChE and VX-BChE reactivation by HTS-identified oximes.
| Compound name | Sarin detoxification kobs × 103 (min−1) [t1/2 (min)] | VX detoxification kobs × 103 (min−1) [t1/2 min] | Sarin-BChE reactivation kobs × 103 (min−1) [t1/2 min] % max react. | VX-BChE reactivation kobs × 103 (min−1) [t1/2 min] % max react. |
|---|---|---|---|---|
| PCM-0211955 | 71 [9.7] | n.a. | 44 [15.7], >95 | 52, [13.3], 85 |
| PCM-0212399 | 133 [5.2] | 1.5, [450] | 7.5, [92], 70 | 35, [19.7], 60 |
| PCM-0211338 | 29 [23.7] | n.a. | 2, [345], 40 | 3, [230], 30 |
| PCM-0211088 | 11 [64.5] | n.a. | 22 [31.4], >95 | 44, [15.7], 87 |
| 2-PAM | 69, [10]a | 9.1, [76]b | 44, [16], 70 | 1.3, [528], 90 |
| HI-6 | 58, [12]a | 42, [16]b | 32, [21.6], 94 | 14, [49], 80 |
| Buffer | ~3.5 [197] | 0.1, [>6,900] | <5% react., 24 h | <5% react., 24 h |
Detoxification of VX and sarin (1 µM) by oxime (0.5 mM), including 2-PAM and HI-6 as controls. Detoxification of sarin was measured with 1 µM sarin and 0.5 mM oxime, 20 mM phosphate, pH 8, 25 °C. In the reactivation experiments [VX] = 1.0 × 10−6 M and [sarin] = 3.0 × 10−6 M were used for BChE inhibition. HuBChE (2.0 × 10−6 M) was incubated with either VX or sarin until reaching a steady 90–95% BChE inhibition, before diluting the OP-BChE conjugate 100-fold into oxime or buffer solution, ([oxime] = 0.5 mM), 10 mM phosphate pH 8.0, 25 °C.
n.a. Not active
aRef. 26 measured with sarin 1.5 mM and 15 µM oxime, 100 mM MOPS, pH 7.4, 25 °C.
bRef. 27.