Table 1 Initial SAR to differentiate TLR inhibition from ER binding affinity.

IC50 and EC50values for TLR9 were obtained using RAW264.7 cells. Values are presented as means ± SD of three independent experiments.


Embedded Image
EntryCompoundR1R3R4R5TLR9TLR9RBA*
IC50 (μM)Toxicity
EC50 (μM)
ERαERβ
1MPPOHEmbedded ImageCH3BSC2.11 ± 0.6413.2 ± 2.412 ± 20.05 ± 0.01
2TSI-13-03OHEmbedded ImageEtEmbedded Image32.1 ± 1.4343 ± 6.48.92 ± 0.530.324 ± 0.01
3TSI-13-30OCH3Embedded ImageCH3BSC1.97 ± 1.7233.2 ± 2.70.013 ± 0.001<0.001
4TSI-13-27OHEmbedded ImageHBSC1.03 ± 0.812.3 ± 3.75.92 ± 0.130.021 ± 0.007
5TSI-13-04OHEmbedded ImageEtBSC2.84 ± 0.1211.6 ± 0.911.5 ± 1.50.49 ± 0.27
6TSI-13-19OHEmbedded ImageEmbedded ImageBSC28.2 ± 0.535.7 ± 4.717.8 ± 5.10.044 ± 0.02
7TSI-13-06OHEmbedded ImageBSCEt3.12 ± 0.10311.2 ± 1.17.34 ± 0.0360.467 ± 0.13
8TSI-13-07OHEmbedded ImageBSCn-Pr2.96 ± 0.212.9 ± 0.38.54 ± 2.11.45 ± 0.05
9TSI-13-05OHBSCEtEmbedded Image3.33 ± 0.27.4 ± 0.40.1320.010

*RBA indicates relative binding affinity values, where estradiol = 100.

†Single determinations.