Interaction of prototypical membrane-permeable P-site inhibitors with mACs, sAC, sGC, and adenosine receptors

AC activity was determined in the presence of Mg2+ and in the presence of stimulators (GαS-GTPγS and/or FSK) to ensure maximum catalytic activity and, hence, highest inhibitor potency possible. For ACs, pIC50 values are listed. For adenosine receptors, pKi values are listed. Structures of P-site inhibitors are shown in Fig. 13. 2′,5′-Dideoxy-3′-ATP (Table 8 and Fig. 15) is mechanistically related to the P-site inhibitors shown here.

AC14.27a, 3.95b, 3.92c4.04a, 3.48b4.31a, 3.86b
AC23.71a, 3.41b, 3.17c, 3.54d3.11a, >3.00b, >3.00e, >3.00d3.61a, 3.26b, 3.15e
AC33.96a, 4.00d4.03a, 3.64e, 3.89d4.07a
AC55.46a, 5.02b, 5.66d5.15a, 4.09b, 4.82e, 5.08d5.67a, 4.70b, 5.00e
AC8>3.00a, 3.92c>3.00a>3.00a
AC9> 3.00a>3.00a>3.00a
Mouse heart AC, wild type5.20b4.37b4.98b
Mouse heart AC, AC5 knockout5.30b4.41b5.00b
Rat heart AC, left ventricleN.D.4.48g4.73g
Rat heart, right ventricleN.D.4.62g5.12g
Adenosine A1 receptor4.86h4.62h>4.00h
Adenosine A2A receptor4.76h5.52h>4.00h
Adenosine A3 receptor>4.22h>4.00h>4.00h
  • N.D., not determined.

  • a Brand et al., 2013.

  • b Braeunig et al., 2013.

  • c Johnson et al., 1997.

  • d Onda et al., 2001.

  • e Iwatsubo et al., 2004.

  • f Bitterman et al., 2013.

  • g Braeunig et al., 2014.

  • h Klotz and Kachler, 2016.