TABLE 6

Inhibition of mACs, sAC, and sGC by (M)ANT- and TNP-nucleotides

Nucleotidyl cyclase activity was determined in the presence of Mn²⁺. Reaction mixtures contained nucleotides analogs at concentrations from 10 nM to 100 μM. Inhibition curves were analyzed by nonlinear regression and were best-fitted to monophasic sigmoidal curves. pK_i values are listed in the table. The structures of the inhibitors examined are shown in Fig. 13. Compounds 1, 3, 7, 10, 11, and 20 were studied at partially purified sAC from rat testis; compounds 22–25 were studied at the purified catalytic domain of human sAC. The Table has been modified from Table 1 in Dove et al. (2014). Data for mACs 1, 2, and 5 and 5C1:2C2 were taken from the literature as noted by the footnotes.

Cpd.	Inhibitor	AC1	AC2	AC5	5C1:2C2	sAC	sGC α₁β₁ (GC1^a)
1	MANT-ATP	6.82^b	6.48^b	7.00^b	7.80^b	5.25^c	6.77
2	MANT-ITP	8.55^b	7.85^b	8.92^b	9.15^b	N.D.	6.31
3	MANT-GTP	7.05^b	6.21^b	7.28^b	7.74^b	>4.00^c	6.06
4	MANT-XTP	5.96^b	5.52^b	5.89^b	5.92^b	N.D.	6.95
5	MANT-CTP	6.82^b	6.16^b	6.82^b	8.04^b	N.D.	6.28
6	MANT-UTP	7.34^b	6.34^b	7.49^b	8.21^b	N.D.	6.30
7	2’-MANT-3′-dATP	6.33^b	6.27^b	7.19^b	7.05^b	4.60^c	7.78
8	3′-MANT-2’-dATP	6.49^b	5.32^b	6.44^b	6.72^b	N.D.	6.13
9	MANT-ATPγS	6.80^d	6.42^d	7.11^d	N.D.	N.D.	6.88
10	MANT-ITPγS	7.39^c	6.92^c	7.51^c	7.72^b	>4.00^c	6.03
11	MANT-GTPγS	7.21^c	6.44^c	7.46^c	7.62^b	>4.00^c	6.33
12	ANT-ATP	6.89^b	6.19^b	6.92^b	7.77^b	N.D.	6.63
13	Cl-ANT-ATP	7.10^e	6.31^e	7.35^e	N.D.	N.D.	7.33
14	Cl-ANT-ITP	8.48^e	8.10^e	8.70^e	N.D.	N.D.	5.92
15	Br-ANT-ITP	8.15^e	7.66^e	8.34^e	N.D.	N.D.	6.22
16	Pr-ANT-ATP	6.36^e	5.96^e	6.44^e	N.D.	N.D.	6.80
17	Pr-ANT-ITP	7.66^e	7.17^e	8.00^e	N.D.	N.D.	6.41
18	AcNH-ANT-ATP	5.17^e	4.96^e	5.47^e	N.D.	N.D.	6.11
19	AcNH-ANT-ITP	6.85^e	6.41^e	7.43^e	N.D.	N.D.	6.22
20	MANT-AppNHp	6.80^c	6.31^c	6.92^c	7.70^c	5.72^c	6.77
21	MANT-GppNHp	6.96^c	6.18^c	7.01^c	7.47^c	N.D.	5.56
22	TNP-ATP	8.05^f	7.00^f	8.43^f	7.09^g	6.19^f	7.67
23	TNP-GTP	7.64^f	6.66^f	7.57^f	7.08^g	5.14^f	7.97
24	TNP-CTP	7.62^f	6.96^f	7.51^f	6.51^g	5.29^f	7.01
25	TNP-UTP	8.15^f	7.62^f	7.82^f	7.04^g	5.51^f	7.29
26	Bis-MANT-ATP	6.15^e	5.68^e	6.37^e	N.D.	N.D.	6.23
27	Bis-MANT-ITP	6.51^e	5.96^e	6.85^e	N.D.	N.D.	6.46
28	Bis-MANT-CTP	6.21^e	5.11^e	6.12^e	N.D.	N.D.	6.10
29	Bis-MANT-IDP	6.00^e	5.85^e	6.15^e	N.D.	N.D.	5.72
30	Bis-MANT-IMP	<3^e	<3^e	<3^e	N.D.	N.D.	<3
31	Bis-Cl-ANT-ATP	5.77^e	5.62^e	5.80^e	N.D.	N.D.	6.28
32	Bis-Cl-ANT-ITP	7.18^e	6.70^e	7.19^e	N.D.	N.D.	6.08
33	Bis-Br-ANT-ATP	N.D.	N.D.	N.D.	N.D.	N.D.	6.37
34	Bis-Br-ANT-ITP	7.68^e	7.15^e	7.82^e	N.D.	N.D.	6.20
35	Bis-Pr-ANT-ATP	4.74^e	4.44^e	4.74^e	N.D.	N.D.	5.44
36	Bis-Pr-ANT-ITP	6.36^e	5.85^e	6.60^e	N.D.	N.D.	5.91
37	Bis-AcNH-ANT-ATP	4.66^e	5.15^e	5.21^e	N.D.	N.D.	5.41
38	Bis-AcNH-ANT-ITP	5.77^e	5.25^e	6.32^e	N.D.	N.D.	5.97

N.D., not determined.
↵^a Dove et al., 2014.
↵^b Pinto et al., 2011.
↵^c Gille et al., 2004.
↵^d Göttle et al., 2009.
↵^e Geduhn et al., 2011.
↵^f Suryanarayana et al., 2009a.
↵^g Mou et al., 2006.