Chemical structure of the three main nephrotoxic acyclic nucleotide analogs, adefovir, cidofovir and tenofovir, as well as less nephrotoxic tenofovir derivatives under development. A lesser uptake by proximal tubular cells can be achieved by either esterifying the compounds with an alkoxyalkyl group, in effect disguising them as lysophospholipids (hexadeciloxypropyl-tenofovir, CMX157) or by ribose-modification (GS-9148 and its oral prodrug GS-9131).