TABLE 3

Experimental nucleoside transporter data and CoMFA predictions Activities are shown as percentage inhibition.

hCNT1(0.1 mM inhibitor, 1 μM[3H]Thymidine) hCNT2(0.1 mM inhibitor, 0.5 μM[3H]Inosine) hENT1(2.0 mM inhibitor, 10 μM[3H]Uridine)
n Inhibitor Activity Prediction Activity Prediction Activity Prediction
1 1-Methyladenosine 59.5 63.7 82 66.3 36.5 34.9
2 2′,3′-Dideoxyadenosine N/M N/M N/M N/M 87.6 86.8
3 2′,3′-Dideoxycytidine 122.1 121.2 N/M N/M 132 133.1
4 2′,3′-Dideoxyuridine 113.6 117.0 98.7 113.5 118.3 115.8
5 2-Chloro-2′-deoxyadenosine (Cladribine) 35.7 37.9 100.7 70.8 14.8 17.7
6 2-Chloroadenosine 50.8 52.9 88.9 76.2 16.4 15.2
7 2′-Deoxyadenosine N/M N/M N/M N/M 22.7 21.8
8 2′-Deoxyuridine 28.4 28.2 36.6 N/P 23.3 27.7
9 2-Fluoro-AF-adenine (Fludarabine) 74.5 N/P 104.2 90.6 N/M N/M
10 3′-Deoxyadenosine N/M N/M N/M N/M 54.6 55.5
11 3-Deazauridine 63.9 69.7 101.9 N/P 97.4 95.7
12 3′-Deoxyuridine 110.7 108.9 105.8 108.3 60 60.0
13 3-Methyluridine 52.3 38.5 53.1 47.4 33.3 33.6
14 4-Thiouridine 17.8 25.0 19.6 28.0 31.8 30.1
15 5-Bromouridine 17.6 23.0 64 65.2 N/M N/M
16 5-(2-Bromovinyl)-2′-deoxyuridine (Brivudin) 16.2 11.5 89.1 105.6 N/M N/M
17 5′-Deoxyadenosine 73.5 N/P 95.9 93.9 29.8 31.7
18 5′-Deoxythymidine 54 57.0 N/M N/M 32.9 29.4
19 5-Fluoro-2′-deoxyuridine (Floxuridine) 28.1 26.3 73.5 95.7 23.6 25.2
20 5-Fluoro-5′-deoxyuridine 65.4 58.7 110.1 99.1 N/M N/M
21 5-Fluorouridine 28.5 37.2 31.2 23.0 29.1 28.0
22 5-Iodo-2′-deoxyuridine (Idoxuridine) 16 19.1 104.4 109.6 39.9 39.3
23 5-Iodouridine 16.1 7.4 101 N/P 20.4 20.7
24 5-(Trifluoromethyl)-2′-deoxyuridine (Trifluridin) 27.1 23.8 103.4 114.0 69.8 69.5
25 6-Azauridine 99.1 82.0 73.2 59.0 88.8 N/P
26 7-Deazaadenosine 42 41.5 61.6 56.9 15.1 16.6
27 8-Bromoadenosine 104.1 98.5 95.8 105.4 20.7 19.0
28 Adenosine 38.2 40.1 8.6 38.5 24.9 25.2
29 Acadesine N/M N/M 73 77.6 58.1 59.1
30 AF-adenine (Vidarabine) 89.3 91.4 99.7 85.8 32.7 34.6
31 AF-cytosine (Cytarabine) 131.4 134.7 N/M N/M 49.7 48.5
32 Cytidine 33.6 28.7 N/M N/M 38.2 35.5
33 2′,3′-Dideoxyinosine N/M N/M 95.7 87.6 126.6 125.7
34 Guanosine N/M N/M 18.2 26.7 35.9 35.4
35 Inosine N/M N/M 7.6 34.7 27.3 30.3
36 Lamivudine 143.3 143.8 N/M N/M 106 103.5
37 N6,N6-Dimethyladenosine 74.3 N/P 97.2 85.8 13.5 13.9
38 N6-Methyladenosine 47 52.1 86.9 81.8 N/M N/M
39 Ribavirin N/M N/M 31 21.4 62.1 61.2
40 Stavudine 126.8 126.9 N/M N/M 121.9 125.8
41 Thymidine 18.5 23.1 N/M N/M 30 27.8
42 Uridine 26.2 32.4 18.3 23.2 29.8 30.5
43 UMP N/M N/M N/M N/M 123 124.1
44 Zidovudine 91.3 92.5 N/M N/M 103 104.5

  • N/M, not experimentally measured; N/P, not predicted (outlier); AF, 9β-d-arabinofuranosyl.