JE-2147 is a new protease inhibitor under development by Agouron, a division of Pfizer. JE-2147 is also known as AG1776 or KNI-764.

It is active in the test tube against HIV which has high level cross-resistance to the currently available protease inhibitors with mutations at codons 82, 48, and 90, and against HIV which carries the D30N resistance mutation associated with resistance to nelfinavir (Yoshimura 1999).

Developers Agouron say that some protease resistance patterns also make HIV hypersusceptible to JE-2147, which means that less of the drug would be needed to achieve a given viral load reduction than in wild type virus. JE-2147 is not susceptible to boosting with ritonavir or other protease inhibitors, and is more active than nelfinavir.

Despite encouraging in vitro data published in 1999, no data has yet been presented from human studies to support these claims.

References

Nash-Alexander T et al. Determination of the in vitro resistance profile of AG-1776, a novel inhibitor of HIV protease. Antiviral Therapy 4 (Supp 1), abstract 19, 1999.

Yoshimura K et al. JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1. Proceedings of the National Academy of Sciences U S A. 96(15):8675-8680, 1999.