Table 3.
Inhibitory activity against Cell-to-Cell HIV transmission by NBD compounds.
| A. Chronically infected cells H9-HIV-1IIIB and Molt-HIV-1ADA were used as donor cells and TZMb-l were used as acceptor cells. | ||
|---|---|---|
| Compound | IC50 (μM)a | |
| TZMb-l/H9-HIV-1IIIB | TZMb-l/Molt-HIV-1ADA | |
| NBD-14107 | 0.56±0.03 | 1.7±0.1 |
| 48 | 0.41±0.07 | 1±0.1 |
| 39 | 0.079±0.003 | 0.44±0.002 |
| 55 | 0.097±0.006 | 0.3±0.02 |
| BMS-626529 | 0.025±0.005 | ~0.4 |
| B. PBMC cells acutely infected with lab-adapted and primary clinical isolates HIV-1 were used as donor cells and TZMb-l were used as acceptor cells. | ||||||
|---|---|---|---|---|---|---|
| Viral Strain | Subtype/coreceptor | IC50 (μM)a | ||||
| NBD-14107 | 48 | 39 | 55 | BMS-626529 | ||
| HIV-193RW018 | A / R5 | 2.5±0.1 | 2.4±0.3 | 0.2±0.006 | 0.18±0.01 | ~0.1 |
| HIV-193RW034 | A / R5 | 0.89±0.07 | 0.87±0.01 | 0.29±0.02 | 0.19±0.01 | ~0.1 |
| HIV-1LAIb | B / X4 | 0.73±0.03 | 0.31±0.01 | 0.21±0.05 | 0.26±0.05 | ~0.1 |
| HIV-189.6b | B / R5X4 | 2.6±0.3 | 0.54±0.1 | 0.25±0.004 | 0.33±0.01 | ~0.1 |
| HIV-1BaLb | B / R5 | 0.64±0.1 | 0.45±0.03 | 0.23±0.01 | 0.33±0.02 | ~0.1 |
| HIV-192US073 | B / R5 | 1.2±0.05 | 0.66±0.05 | 0.22±0.01 | 0.16±0.001 | ~0.1 |
| HIV-192US657 | B / R5 | 3.6±0.2 | 1.2±0.08 | 0.59±0.05 | 0.71±0.03 | ~0.1 |
| HIV-193BR019 | BF/ X4 | 1.9±0.16 | 0.25±0.04 | 0.31±0.01 | 0.2±0.006 | ~0.1 |
| HIV-1CMU02 | EA / X4 | 4.5±0.3 | 4.2±0.5 | 1.87±0.01 | 1.1±0.14 | >6 |
| HIV-1Ru132 | G / R5 | 0.84±0.1 | 0.57±0.03 | 0.33±0.1 | 0.3±0.02 | ~0.1 |
| HIV-1RU570 | G / R5 | 1.3±0.1 | 0.28±0.006 | 0.37±0.004 | 0.32±0.01 | ~0.1 |
| HIV-1BCF01 | O / R5 | 0.96±0.06 | 0.31±0.03 | 0.28±0.06 | 0.22±0.01 | >6 |
| HIV-1BCF03 | O / R5 | 2.2±0.06 | 0.71±0.05 | 1.6±0.08 | 0.18±0.01 | >6 |
| Mean ± SEM (μM): (n=13) | 1.84±0.3 | 0.98±0.3 | 0.52±0.15 | 0.34±0.07 | - | |
| Toxicity in-infected PBMC : CC50 (μM) | >60 | ~61 | ~61 | 38.7±3.8 | >10 | |
The reported IC50 values represent the means ± standard deviation (SD), n=3.
The reported IC50 values represent the means ± standard deviation (n = 3).
Laboratory-adapted virus; all the rest are clinical isolate viruses