 |
|
|
| |
BMS-766, a Novel HCV NS5A Inhibitor With Enhanced Resistance Coverage
|
| |
| |
Reported by Jules Levin
EASL 2011 Berlin March 30-April 2
Gao M, Fridell R, Wang C, Sun J-H, O'Boyle II DR, Valera L, Nower P, Monikowski A, Kirk M, Huang H, Ngo CK, Fang H, Knox R, Wang Y-K, Nguyen VN, Yang F, Snyder LB, Lavoie R, Bender JA, Kadow JF, Cockett M, Meanwell NA, Belema M
Bristol-Myers Squibb, Research and Development, Wallingford, CT, USA
BACKGROUND
NS5A inhibitors are a new class of potent anti -hepati ti s C virus (HCV) agents identi fied by Bristol-Myers Squibb (BMS) (Table 1)
- BMS-790052 is a replicati on complex inhibitor, with EC50 values of 50 and 9 pM
against genotype (GT) 1a and 1b replicons, that exhibits broad genotype coverage
-- The potency of BMS-790052 against GT1a and 1b replicons translated to rapid viral decline in clinical studies1
The NS5A protein is a key component of the HCV replication complex4
BMS NS5A inhibitors disrupt active viral RNA replication (Figure 1)
Our current hypothesis is that these interacti ons with the replicati on complex deliver the exceptional potency of BMS NS5A inhibitors
References
1. Pol S, et al. 45th EASL; April 14-18, 2010; Vienna, Austria. Abstract 1189.
2. Lenz O, et al. Anti microb Agent Chemother 2010;54:1878-1887.
3. Clark JL, et al. J Med Chem 2005;48:5504-5508.
4. Reiss S, et al. Cell Host Microbe 2011;9:32-45.
5. Colonno R, et al. 45th EASL; April 14-18, 2010; Vienna, Austria. Abstract 33.
6. Gao M, et al. 61st AASLD, October 29-November 2, 2010; Boston, MA, USA.
Abstract 1853.
7. Gao M, et al. Nature 2010; 465:96-100.
|
| |
|
|
|
|
|
