Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates

Table 2 Functional EC₅₀ values for nucleoside monomers and dendrimer conjugates to activate the A₁ AR ([³⁵S]GTPγS binding and cAMP inhibition) and A₃ AR (cAMP inhibition).^a

Compound	A₁ ([³⁵S]GTPγS binding), EC₅₀ (nM)	A₁ (adenylyl cyclase), EC₅₀ (nM)	A₃ (adenylyl cyclase), EC₅₀ (nM)
Nucleoside Monomers
1	94 ± 26	400 ± 80	100 ± 50
4	1300 ± 400	350 ± 20	140 ± 70
7	63 ± 14	89 ± 17	36 ± 13
Dendrimer Derivatives
11	50%^b	inactive^c	inactive^c
12	190 ± 70	23 ± 10	25 ± 10
13	940 ± 70	54 ± 20	17 ± 2
15	< 10%^b	inactive^c	inactive^c
16	2400 ± 1300	120 ± 1	14 ± 5
17	370 ± 190	260 ± 90	1.6 ± 0.4

a. All experiments were performed using adherent CHO cells stably expressing the A₁ or A₃ AR. Binding of [³⁵S]GTPγS and assays using a cAMP kit were carried out as described in methods. Values are expressed as EC₅₀ values (mean ± SEM, n = 3) or as displacement of the radioligand at 10 μM. b. Percent of [³⁵S]GTPγS binding at 10 μM compared to full agonist. c. Compound produced less than 20% of total inhibition at 10 μM as seen by ADAC.

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