Table 1. Structure activity relation (SAR) analysis for PKA holoenzyme activation.
| PKA holoenzyme complex | Ligand | EC50 (95% Cl)* |
|---|---|---|
| T. brucei PKAR/PKAC1 | Inosine | 14 (13–15) nM |
| Guanosine | 152 (132–172) nM | |
| Adenosine | 7.0 (6.9–8.4) µM | |
| cAMP | -† | |
| cGMP | 0.36 (0.33–0.41) mM | |
| cIMP | -† | |
| AMP | -† | |
| GMP | 1.1 (0.9–1.3) mM | |
| IMP | 108 (83–135) µM | |
| 2'-deoxyadenosine | -† | |
| 3'-deoxyadenosine | -† | |
| 5'-deoxyadenosine | -† | |
| Nebularine | 2.6 (2.2–3.2) µM | |
| Allopurinol riboside | 1.7 (1.5–1.9) µM | |
| Xanthosine | 62 (51–72) µM | |
| Uridine | 40 (35–47) µM | |
| Cytidine | ≥350 µM | |
| Leishmania PKAR1/PKAC1 | Inosine | 47 (33–63) nM |
| Guanosine | 1.7 (1.4–2.1) µM | |
| Adenosine | 6.5 (5.7–7.6) µM | |
| cAMP | -† | |
| T. cruzi PKAR/PKAC2 | Inosine | 150 (110–200) nM |
| Guanosine | 3.5 (2.8–4.5) µM | |
| Adenosine | 8.3 (5.2–12.4) µM | |
| cAMP | -† | |
| human RIα/mouse Cα | Inosine | -† |
| Guanosine | -† | |
| Adenosine | -† | |
| cAMP | 75 (59–93) nM |
*
Mean half activation constants (EC50) and 95% confidence interval (95% CI) determined from Figure 1—figure supplement 1 using Graphpad prism 7.0 for technical triplicates.
†
No activation was detected up to a maximum concentration of 5 mM.