TABLE 5.
Sensitivity of viruses resistant to HIV-1-specific inhibitors to SJ-3366
| Resistant isolate (mutation)b | IC50 (μM
[fold resistance])a
|
||
|---|---|---|---|
| SJ-3366 | Nevirapine | AZT | |
| IIIB (control) | 0.002 | 0.01 | 0.05 |
| Oxathiin carboxanilide (L100I) | 0.008 (S) | 0.1 (10) | 0.04 |
| TSAO-costatolide (K101E) | 0.05 (18) | 0.4 (40) | 0.004 |
| UC10-costatolide (K103N) | >0.14 (>50) | >10 (>1000) | 0.003 |
| Thiazolobenzimidazole (V108I) | 0.05 (18) | 0.3 (30) | 0.04 |
| TIBO-R82150 (A98G/V108I) | 0.1 (70) | 0.6 (60) | 0.05 |
| Calanolide A (T139I) | 0.01 (S) | 0.01 (S) | 0.01 |
| Diphenylsulfone (Y181C) | >0.1 (>50) | 5.9 (590) | 0.01 |
| Nevirapine (Y181C) | 0.085 (100) | >38 (>3,800) | 0.03 |
| Pyridinone (Y181C/L103N) | 0.4 (180) | >38 (>3,800) | 0.01 |
| E-BPTU (Y181C) | 0.8 (375) | 1.9 (190) | 0.03 |
| UC38 (Y181C) | 0.02 (10) | 1.9 (190) | 0.01 |
| 3TC (M184V) | 0.0006 (S) | 0.01 (S) | 0.02 |
| Costatolide (Y188H) | 0.1 (55) | NDc | 0.004 |
| HEPT (P236L) | 0.028 (33) | 0.02 (S) | 0.01 |
The results presented were obtained from a single representative antiviral assay, with appropriate nevirapine and AZT control values selected from a minimum of two antiviral assays. We have demonstrated that the standard error between multiple antiviral assays averaged less than 10% of the respective mean IC50. Fold resistance values were calculated by determination of the ratio of the activity of each compound against the drug-resistant virus isolate to the activity against wild-type isolate IIIB (control) performed in parallel. Fold resistance values indicated as greater than indicate that the compound was inactive at the greatest nontoxic concentration tested; S, the virus remained sensitive to the agent.
TSAO, [2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-spiro-5"-(4"-amino-1",2"-oxathiole-2", 2"-dioxide)]-β-d-pentofuranosyl; TIBO, tetrahydro-imidazo-[4,5,1-jk][1,4]-benzodiazepin-2(M)-thione.
ND, not determined.