TABLE 1

Potencies of Amlexanox Analogs

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Compound No.RcLogPaTBK1 IC50 (µM)bIKKε IC50 (µM)bSelectivity for IKKεc
1 (Amlexanox)–COOH3.650.8 ± 0.15.8 ± 0.80.2
3–COOEt4.3655 ± 29***65 ± 47***0.8
4–CH2OH2.5824 ± 5.7***18 ± 8.21.3
5aEmbedded Image3.432.9 ± 0.51.6 ± 0.41.8
5bEmbedded Image3.07>100***17 ± 13>5.9
5cEmbedded Image3.8036 ± 14***14 ± 8.62.6
5dEmbedded Image2.8773 ± 26***57 ± 23***1.3
6Embedded Image4.024.5 ± 0.8**5.4 ± 2.00.8
7–H3.3533 ± 18***2.6 ± 1.113
9Embedded Image3.220.4 ± 0.050.2 ± 0.03***2.0
11Embedded Image3.042.9 ± 1.01.6 ± 0.71.8
12Embedded Image3.39>100***>100***1
  • a Calculated partitioning coefficient (calculated via Marvin, ChemAxon). Larger values suggest enhanced cellular permeability.

  • b In vitro potency (IC50) toward TBK1 and IKKε (n = 3, mean ± S.E.M.). Statistical significance from amlexanox determined by two-way ANOVA with Dunnett’s multiple comparison correction. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001.

  • c Selectivity determined by diving mean TBK1 IC50 by the mean IKKε IC50.