Tenofovir exalidex (CMX 157) is a lipid-conjugated acyclic nucleotide analog of Tenofovir, demonstrating efficacy against wild-type and antiretroviral-resistant HIV strains, including those resistant to multiple nucleoside/nucleotide analogs. It effectively inhibits all major HIV-1 and HIV-2 subtypes in fresh human PBMCs, as well as all evaluated HIV-1 strains in monocyte-derived macrophages, displaying EC50 values between 0.2 and 7.2 nM. Oral administration of CMX157 shows no apparent toxicity. Additionally, Tenofovir exalidex exhibits antiviral properties against HBV.

Tenofovir exalidex demonstrates over 300-fold greater activity than Tenofovir against a broad spectrum of viruses across various cell systems and shows efficacy against MNR mutants resistant to all current NRTIs. Particularly, in PBMCs, CMX157 exhibits an average EC50 of 2.6 nM (ranging from 0.2 to 7.2 nM) against 27 wild-type HIV-1 isolates from group M subtypes A to G and group O[1]. The mechanism of action involves inhibiting HBV polymerase to prevent HBV DNA elongation, without the involvement of cyclophilins in this process. Moreover, the combination of CRV431 (host-targeting) and Tenofovir exalidex (direct-acting) leads to a synergistic effect in inhibiting HBV DNA synthesis, indicating their actions target different stages of the HBV life cycle[3].

Tenofovir exalidex (Sprague-Dawley rats) is orally available and shows no apparent toxicity at 10, 30, or 100 mg/kg/day doses for 7 days[2]. It decreases liver HBV DNA levels dose-dependently when administered via oral gavage at 5-10 mg/kg daily for 16 days[3].