UNC10217938A HCl (UNC7938 HCl) is a 3-deazapteridine analog. UNC10217938A HCl exhibits strong oligonucleotide enhancing effects. UNC10217938A HCl can modulate their intracellular trafficking and release from endosomes, leading to enhance oligonucleotides effects. UNC10217938A HCl also enhances the effects of siRNA and antisense oligonucleotides.

UNC10217938A HCl strongly enhances luciferase induction in HelaLuc705 cells when used in the 5-25 µM range and are substantially more effective and potent than Retro-1. As compared to splice switching oligonucleotide (SSO) alone, UNC10217938A HCl provids a 60-fold enhancement at 10 µM and 220-fold at 20 µM, in contrast to a 11-fold enhancement for 100 µM Retro-1[1]. UNC10217938A HCl can substantially enhance effects of receptor targeted oligonucleotide conjugates. UNC10217938A HCl also can enhance effects of uncharged morpholino oligonucleotides as well as negatively charged oligonucleotides[1]. Exposure of cells to UNC10217938A HCl leads to a major reduction in co-localization of the TAMRA-oliogonucleotide with the late endosome marker Rab7, but had little effect on co-localization with the lysosomal marker LAMP-1. UNC10217938A HCl causes partial release of oligonucleotide from late endosomes to the cytosol followed by nuclear accumulation[1].

Systemic treatment with SSO623 followed by administration of UNC10217938A HCl (7.5 mg/kg; intravenous injection) produces distinct increases in EGFP fluorescence in liver, kidney and heart in EGFP654 mice[1].