TABLE 2

Solubility and Potencies of Amlexanox Analogs Against Kinase Variants

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Compound#1 (Amlexanox)91112
R–COOHEmbedded ImageEmbedded ImageEmbedded Image
Solubility (mg ml−1)a≥20≥2.5<1<<0.5
IC50 (µM)b
TBK10.8 ± 0.10.4 ± 0.052.9 ± 1.0>100
TBK1 T156A10 ± 1.5***0.06 ± 0.061.9 ± 1.4n.i.
IKKε5.8 ± 0.80.2 ± 0.031.6 ± 0.7>100
IKKε M86L1.1 ± 1.0***0.03 ± 0.020.04 ± 0.03*n.i.
IKKε T156A1.9 ± 1.4***0.02 ± 0.010.3 ± 0.2*n.i.
  • n.i., no inhibition up to 200 µM.

  • a Thermodynamic solubility determined by first dissolving each compound at a basic pH (dilute NaOH solution) and adjusting to pH 7.4–7.6 with buffer.

  • b In vitro potency (IC50, µM) toward TBK1 and IKKε variants (mean ± S.E.M., n = 3). TBK1 M86L did not express in insect cells. Statistical significance relative to wild-type variant determined via two-way ANOVA with Bonferroni correction for multiple comparisons (*P < 0.05; ***P < 0.001).