UNC10217938A is a 3-deazapteridine analog that is effective in enhancing the actions of oligonucleotides with low cytotoxicity [1]. UNC10217938A markedly promotes the activity of ASOs, siRNAs, and splice-switching oligonucleotides by permeabilizing endosomes and lysosomes [2]. UNC10217938A can enhance the endosome escape of the cell-penetrating peptide containing Cre recombination protein (TATCre) and improve the functional delivery of TATCre to target cells[3]. UNC10217938A has been widely used as an oligonucleotide enhancer compound (OEC) to enhance the cellular permeability of drug-like oligonucleotides[4].
References:
[1] Yang B, Ming X, Cao C, et al. High-throughput screening identifies small molecules that enhance the pharmacological effects of oligonucleotides[J]. Nucleic acids research, 2015, 43(4): 1987-1996.
[2] Finicle B T, Eckenstein K H, Revenko A S, et al. Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics[J]. Nucleic Acids Research, 2023, 51(4): 1583-1599.
[3] Heath N, Osteikoetxea X, de Oliveria T M, et al. Endosomal escape enhancing compounds facilitate functional delivery of extracellular vesicle cargo[J]. Nanomedicine, 2019, 14(21): 2799-2814.
[4] Batistatou N, Kritzer J A. Comparing cell penetration of biotherapeutics across human cell lines[J]. ACS chemical biology, 2024, 19(6): 1351-1365.
UNC10217938A是一种3-deazapteridine类似物，能够有效增强寡核苷酸的作用，且细胞毒性低[1]。UNC10217938A通过增加内体和溶酶体的通透性，显著增强ASOs、siRNAs和剪接转换寡核苷酸的活性[2]。UNC10217938A能增强含Cre重组蛋白的细胞穿透肽（TATCre）的内体逃逸，并改善TATCre向靶细胞的功能性递送[3]。UNC10217938A已被广泛用作寡核苷酸增强剂化合物（OEC），以增强药物样寡核苷酸的细胞通透性[4]。