GS-9770 is a potent, selective, non-peptidomimetic and orally active HIV protease inhibitor with Ki(app) value of 0.16 nM (recombinant HIV-1 PR).
GS-9770 substantially reduces Gag polyprotein cleavage and the concomitant release of mature p24 protein at 10 nM, with complete inhibition of p24 formation at 100 nM in virus-producing HEK293T cells.
GS-9770 shows high antiviral potency identical to that of atazanavir (ATV), with a mean 50% effective concentration (EC50) value of 11 nM for MT-4 cells acutely infected with the syncytia-inducing HIV-1 IIIb strain.
GS-9770 exhibitsmean EC50 value of 8.5 nM in primary human immune target cells acutely infected with HIV-1 BaL strain using a virus (p24) production assay.
GS-9770 maintainshigh antiviral potency (EC50 range of 1.9 to 26 nM) against HIV-1 and HIV-2.
Combinations of GS-9770 with the NRTIs tenofovir alafenamide (TAF) or FTC, the NNRTI rilpivirine (RPV), the INSTI bictegravir (BIC), or the capsid inhibitor lenacapavir (LEN) resulted in highly synergistic anti-HIV activity with mean synergy volumes ranging from 163 to 180 µM.