TABLE 3.
SAR progression toward clinical candidate BMS-955176: coverage of Gag/Pr libraries derived from subtype B clinical isolatesa
| Key singlea polymorphism(s)b | nc | EC50, nM |
BMS-955176 |
|||
|---|---|---|---|---|---|---|
| BVMc | BMS-2c | BMS-3c | n | EC50, nMd | ||
| None (WT) | 21 | 14 | 14 | 3 | 51 | 3 |
| V362I | 3 | 36 | 29 | 6 | 5 | 5 |
| Q369H | 1 | 4 | 7 | 15 | 1 | 2 |
| V370I/L/T | 3 | 251 | 26 | 10 | 4 | 3 |
| V370A | 3 | 227 | 38 | 12 | 7 | 2 |
| V370 M | 5 | 903 | 76 | 67 | 9 | 7 |
| T371A/Q/N/S/TT | 4 | 113 | 49 | 7 | 6 | 4 |
| V370A + ΔT371 | 3 | >4,000 | 629 | 236 | 4 | 12 |
a
WT, no change at Gag amino acid position V362, Q369, V370, or T371 relative to HXB2; SAR: structural-activity relationship. Values are means from experiments performed in triplicate; coefficients of variation for all experiments were ≤200%.
b
Key single polymorphisms are amino acids not in consensus (HIV-1 HXB2) at one of four Gag positions (V362, Q369, V370, and T371), with concurrent HXB2 amino acids at remaining three positions.
c
Sublibrary, n = 43/87 (column 2).
d
EC50 values are means.