Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates

Table 1 K_i apparent values for binding of nucleoside monomers and dendrimer conjugates at A₁, A_2A, and A₃ ARs.^a

Compound	A₁ K_i (nM)	A_2A K_i (nM)	A₃ K_i (nM)
Nucleoside Monomers
1	10.4 ± 3.8	370 ± 100	12.2 ± 4.1
4 ^d	30 ± 9	800 ± 360	74 ± 20
7 ^d	43 ± 5	300 ± 20	9.5 ± 2.0
Dendrimer Derivatives
11	NB^b	(20 ± 7%)^c	(26 ± 3%)^c
12	21 ± 5	250 ± 40	27 ± 2
13	55 ± 10	405 ± 170	42 ± 17
15	NB^b	NB^b	NB^b
16	175 ± 60	610 ± 110	14.0 ± 2.1
17 ^d	320 ± 20	470 ± 50	2.4 ± 0.4

a. All experiments were performed using adherent CHO cells stably expressing the A₁ or A₃ AR or HEK cells stably expressing A_2A AR. Binding was carried out as described in methods using [³H]CCPA, [³H]CGS21680, or [¹²⁵I]AB-MECA. Values are expressed as K_i values (mean ± SEM, n = 3) or as displacement of the radioligand at 10 μM. b. NB, No binding. Inhibition of radioligand binding < 10% at 10 μM. c. Percent inhibition of radioligand binding at 10 μM. d. 4, MRS5145; 7, MRS5169; 17, MRS5183.

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