Table 1.

Potency of nucleoside-dendrimer conjugates at three subtypes of human ARs.^a

Compound	Ki, hA1 (nM)	Ki, hA2A (nM)	Ki, hA3 (nM)
Monomers
Cl-IB-MECAb	260 ± 60	2300 ± 100	0.29 ± 0.04
5b	>10,000	7040 ± 1430	29.4 ± 9.8
Dendrimer derivatives
1b,c	7.1	5750 ± 1600	17.6 ± 2.8
2b,c	22.6 ± 6.9	32.2 ± 6.4	0.14 ± 0.09
4d	NA	NA	NA
6d	240 ± 70	220 ± 40	2.11 ± 0.51
7	450	190 ± 30	2.57 ± 0.29

^aAll experiments were done on CHO or HEK293 (A_2A only) cells stably expressing one of four subtypes of human ARs. The binding affinity for A₁, A_2A, and A₃ARs was expressed as K_i values (n = 3–5) and was determined by using agonist radioligands ([³H]R-PIA, [³H]CGS21680, or [¹²⁵I]I-AB-MECA, respectively), unless noted. A percentage in parentheses refers to inhibition of radioligand binding at the indicated concentration. The concentrations of the dendrimer-ligand complexes were measured by the concentration of the dendrimer, not the ligand. Therefore, all binding K_i values of dendrimers are expressed as K_iapp values.

^bAffinity values from Tosh et al. [25,26].

^c1, MRS5216; 2, MRS5246; 6, MRS5539; 7, MRS5538.

^dCompound 4 is the dendrimer precursor of 6. Compound 6 is the precursor of 7. NA – not active in inhibition of radioligand binding (<10%) at 1 μM.