TABLE 7

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 (Gα_S-GTP_γ_S 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.

AC	SQ22,536	NKY80	Vidarabine
AC1	4.27^a, 3.95^b, 3.92^c	4.04^a, 3.48^b	4.31^a, 3.86^b
AC2	3.71^a, 3.41^b, 3.17^c, 3.54^d	3.11^a, >3.00^b, >3.00^e, >3.00^d	3.61^a, 3.26^b, 3.15^e
AC3	3.96^a, 4.00^d	4.03^a, 3.64^e, 3.89^d	4.07^a
AC4	3.55^a	3.95^a	4.03^a
AC5	5.46^a, 5.02^b, 5.66^d	5.15^a, 4.09^b, 4.82^e, 5.08^d	5.67^a, 4.70^b, 5.00^e
AC6	5.25^a	4.80^a	5.34^a
AC7	3.38^a	3.09^a	3.64^a
AC8	>3.00^a, 3.92^c	>3.00^a	>3.00^a
AC9	> 3.00^a	>3.00^a	>3.00^a
5C1:2C2	N.D.	N.D.	N.D.
sAC	>>3.00^f	>>3.00^f	>>3.00^f
sGC	N.D.	N.D.	N.D.
Mouse heart AC, wild type	5.20^b	4.37^b	4.98^b
Mouse heart AC, AC5 knockout	5.30^b	4.41^b	5.00^b
Rat heart AC, left ventricle	N.D.	4.48^g	4.73^g
Rat heart, right ventricle	N.D.	4.62^g	5.12^g
Adenosine A₁ receptor	4.86^h	4.62^h	>4.00^h
Adenosine A_2A receptor	4.76^h	5.52^h	>4.00^h
Adenosine A₃ receptor	>4.22^h	>4.00^h	>4.00^h

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.