Table 5.
Summary of electrophilic compounds 8a–f: Yield, IC50 values of the inhibition between coregulatory peptide SRC2-2 and TRα/TRβ, viability (LD50) of U2OS and ARO cells in the presence of compound, solubility in PBS buffer containing 5% DMSO, and permeability across an artificial membrane (PAMPA).
In vitro Potency | Cytotoxicity | Pharmacological Properties | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Entry | R = 4-hexylbenzene | Compound | Yielda (%) | TRαb IC50 (μM) | TRβb IC50 (μM) | TRα: TRβ ratio | AROc LD50 (μM) | U2OSc LD50 (μM) | Solubility (μM) | Permeability (10−6 cm/s) |
1 |
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8a | 63 | 68.9 | 35.1 | 2.0 | 8.0 | 17.1 | 60 | 621 |
2 |
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8b | 57 | 16.7 | 6.2 | 2.7 | 7.9 | 13.9 | 18 | 21 |
3 |
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8c | 84 | 47.7 | 23.1 | 2.1 | 12.2 | 8.3 | 103 | 1029 |
4 |
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8d | 41 | >100 | >100 | - | 2.4 | 69 | 95 | 974 |
5 |
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8e | 69 | 4.2 | 3.0 | 1.4 | 40.1 | 17 | 85 | 1190 |
6 |
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8f | 95 | >100 | >100 | - | 28.7 | 25.3 | 26 | 58 |
7 |
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8g | 74 | 33.2 | 19.1 | 1.7 | >200 | 58 | 204 | 1117 |
Isolated yield;
values are means of two independent experiments done in quadruplicate; the general error limits are 10%;
values are means of two independent experiments done in triplicate; the general error limits are 10–15%. Actual error values for each measurement are omitted for clarity but are included in tables in the supplemental materials.