TABLE 4

Functional cooperativity estimates for the interaction between BETP or Compound 2 and Boc5, TT15, or BMS21

Data derived from analysis of interaction dose-response curves with an operational model of allosterism as defined in eq. 4. Log αβ represents the composite cooperativity between the allosteric ligand and the orthosteric peptide ligand. Antilogarithms are shown in parentheses. Values represent the mean ± S.E.M. of four to six independent experiments performed in duplicate. Data were analyzed with one-way analysis of variance and Dunnett’s post test.

Log αβ (αβ)
Compound 2BETP
Boc50.84 ± 0.39 (6.9)*1.28 ± 0.44 (19)*
TT151.89 ± 0.41 (78)*1.66 ± 0.28 (46)*
BMS212.09 ± 0.35 (123)*2.75 ± 0.22 (562)*
  • BETP, 4-(3-benzyloxyphenyl)-2-ethylsulfinyl-6-(trifluoromethyl)pyrimidine; Boc5, 1,3-bis [[4-(tert-butoxy-carbonylamino)benzoyl]amino]-2,4-bis[3-methoxy-4-(thiophene-2-carbonyloxy)-phenyl]cyclobutane-1,3-dicarboxylic acid; Compound 2, 6.7-dichloro-2-methylsulfonyl-3-tert-butylaminoquinoxaline; TT15, (2S)-2-[[(8S)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid.

  • * P < 0.05.