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. Author manuscript; available in PMC: 2017 Sep 22.
Published in final edited form as: J Med Chem. 2016 Sep 2;59(18):8381–8397. doi: 10.1021/acs.jmedchem.6b00748

Table 3.

In Vitro and in Silico Binding Affinities and Specific Contacts of Mitragynine and Derivatives

compd in vitro Ki (nM) in silico Ki (nM) nonspecifica in silico Ki (nM) specificb receptor side chains in polar contact with the ligand receptor side chains in nonpolar contact with the ligand
mu 1   230 ± 47   23   569 Gln124, Tyr128, Asp147, Tyr326 Met151, Trp293, Ile296, Ile322
2     37 ± 4     4.0     55 Asp147, Lys233, Trp293 Tyr148, Met151, Leu219, Leu232, Ile296
3  0.75 ± 0.18     2.5       2.5 Asp147, Tyr148, Lys233 Ile144, Leu219, Leu232, Trp293, Ile296, His297
delta 1 1011 ± 49 159 1565 Gln105, Lys108, Asp128, Tyr129, Tyr129 Leu128, Lys214 (aliphatic chain), Val217
2     90 ± 8   19     19 Asp128, Tyr129 Met132, Lys214 (aliphatic chain), Val217, Trp274, Ile277, Ile304
3       3 ± 1.3   17     17 Asp128, Tyr129 Met132, Lys214 (aliphatic chain), Val217, Trp274, Ile277, Val281
kappa 1   231 ± 21   17     69 Asp138, Tyr139, Ser211 Trp124, Val134, Leu135
2   131 ± 7     8.3     53 Thr111, Asp138, Tyr139, Lys227, Tyr312, Tyr320 Gln115, Leu135, Ile294
3     24 ± 9     3.2     23 Gln115, Asp138, Tyr139, Ser211, Tyr312 Phe114, Val118, Ile294, Ile316
a

Inhibitory constants calculated for the lowest energy docked complexes including nonspecifically bound poses.

b

Inhibitory constants calculated for the lowest energy docked complexes excluding low energy poses which were regarded as false positives.