KP-1212, also known as SN-1212, is a nucleoside designed for the treatment of HIV by viral mutagenesis.
1:Bioorg Med Chem. 2013 Nov 15;21(22):7222-8. doi: 10.1016/j.bmc.2013.08.023. Epub 2013 Aug 20. 5,6-Dihydro-5-aza-2/'-deoxycytidine potentiates the anti-HIV-1 activity of ribonucleotide reductase inhibitors.Rawson JM,Heineman RH,Beach LB,Martin JL,Schnettler EK,Dapp MJ,Patterson SE,Mansky LM, PMID: 24120088 PMCID: PMC3930610 DOI: 10.1016/j.bmc.2013.08.023
Abstract: The nucleoside analog 5,6-dihydro-5-aza-2/'-deoxycytidine (KP-1212) has been investigated as a first-in-class lethal mutagen of human immunodeficiency virus type-1 (HIV-1). Since a prodrug monotherapy did not reduce viral loads in Phase II clinical trials, we tested if ribonucleotide reductase inhibitors (RNRIs) combined with KP-1212 would improve antiviral activity. KP-1212 potentiated the activity of gemcitabine and resveratrol and simultaneously increased the viral mutant frequency. G-to-C mutations predominated with the KP-1212-resveratrol combination. These observations represent the first demonstration of a mild anti-HIV-1 mutagen potentiating the antiretroviral activity of RNRIs and encourage the clinical translation of enhanced viral mutagenesis in treating HIV-1 infection.