Tenofovir exalidex(CMX157) (Synonyms: Tenofovir exalidex(CMX157))

Tenofovir exalidex (CMX157) is a lipid conjugate of the acyclic nucleotide analog Tenofovir with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. Tenofovir exalidex is active against all major subtypes of HIV-1 and HIV-2 in fresh human PBMCs and against all HIV-1 strains evaluated in monocyte-derived macrophages, with EC50s ranging between 0.2 and 7.2 nM. CMX157 is orally available and has no apparent toxicity. Tenofovir exalidex also shows antiviral activity against HBV.

Tenofovir exalidex is consistently >300-fold more active than Tenofovir against multiple viruses in several different cell systems. Tenofovir exalidex will be effective against MNR mutants, including those that are unresponsive to all currently available NRTIs. Notably, the average EC₅₀ in PBMCs for CMX157 against a panel of 27 wild-type HIV-1 isolates representing group M subtypes A to G and group O was 2.6 nM (range, 0.2 to 7.2 nM)^[1].
Tenofovir exalidex exerts its therapeutic actions by inhibiting HBV polymerase-mediated HBV DNA elongation, but there is no known binding of cyclophilins to HBV polymerase nor participation of cyclophilins in DNA elongation. The combinational effect of CRV431 (host-targeting) and Tenofovir exalidex (direct-acting) on HBV DNA production is more consistent with the two compounds acting on distinct steps of the HBV life cycle^[3].

Tenofovir exalidex (Sprague-Dawley rats) is orally available and has no apparent toxicity when given orally to rats for 7 days at doses of 10, 30, or 100 mg/kg/day^[2].Tenofovir exalidex (5-10 mg/kg; oral gavage; daily for a period of 16 days) decreases liver HBV DNA levels dose-dependently^[3].

[1]. Lanier ER, et al. Development of hexadecyloxypropyl tenofovir (CMX157) for treatment of infection caused by wild-type and nucleoside/nucleotide-resistant HIV. Antimicrob Agents Chemother. 2010;54(7):2901-2909. 

[2]. Gallay P, et al. The cyclophilin inhibitor CRV431 inhibits liver HBV DNA and HBsAg in transgenic mice. PLoS One. 2019;14(6):e0217433. Published 2019 Jun 10. 

[3]. Painter GR, et al. Evaluation of hexadecyloxypropyl-9-R-[2-(Phosphonomethoxy)propyl]- adenine, CMX157, as a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections [published correction appears in Antimicrob Agents Chemother. 2007 Dec;51(12):4538]. Antimicrob Agents Chemother. 2007;51(10):3505-3509.