GS-8374 (TMC-126)

GS-8374 (formerly TMC-126) is a protease inhibitor being developed by Gilead Sciences. It adds a phosphonate group onto a protease inhibitor; the corresponding prodrug is able to enter the cell and entrap the protease enzyme. 

When it was compared in vitro to darunavir, atazanavir, and lopinavir, its activity, resistance, and toxicity profile was superior. It is able to inhibit HIV in infected T-cells lines, primary CD4+ lymphocytes, and macrophages.1

Further, it does not seem to affect the host aspartic proteases.2 Like atazanavir, it does not affect insulin-stimulated glucose uptake in differentiated adipocytes in vitro. According to investigators, it is conceivable that the adverse effects of protease inhibitors on insulin activity can be avoided.2

References

  1. Callebaut C et al. Profile of GS-8374, a novel phosphonate-containing HIV PI: in vitro antiretroviral activity, toxicity, and resistance. 15th Conference on Retroviruses and Opportunistic Infections, Boston, abstract 491, 2008
  2. Callebaut C et al. GS-8374, a novel HIV protease inhibitor, does not alter peripheral glucose disposal in a healthy rodent model system. 15th Conference on Retroviruses and Opportunistic Infections, Boston, abstract 732, 2008
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