Tenofovir exalidex (C09-1183-026)

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 EC 50 s ranging between 0.2 and 7.2 nM. CMX157 is orally available and has no apparent toxicity. Tenofovir exalidex also shows antiviral activity against HBVIn VitroTenofovir 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 EC 50 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). 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoTenofovir 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./nTenofovir exalidex (5-10 mg/kg; oral gavage; daily for a period of 16 days) decreases liver HBV DNA levels dose-dependently. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female transgenic mice HBV transgenic Tg05 mice (C57BL/6) Dosage: 5 mg/kg, 10 mg/kg Administration: Oral gavage; daily for a period of 16 days Result: The reductions in HBV DNA were 55% and 97% for low-dose (5 mg/kg/day) and high-dose (10 mg/kg/day), respectively.Form:SolidIC50& Target:HIV-1 HIV-2. Molecular Formula: C28H52N5O5P Molecular Weight: 569.73 PubChem CID: 23628250 Isomeric SMILES: CCCCCCCCCCCCCCCCOCCCOP(=O)(CO[C@H](C)CN1C=NC2=C(N=CN=C21)N)O