UNC10217938A

• CAT Number: I015484
• CAS Number: 1347749-97-6
• Molecular Formula: C26H28N6O2
• Molecular Weight: 456.54
• Purity: ≥95%
• Synonyms: ethyl N-[8-[2-(dimethylamino)ethylamino]-2,3-diphenylpyrido[2,3-b]pyrazin-6-yl]carbamate
• InChI: InChI=1S/C26H28N6O2/c1-4-34-26(33)29-21-17-20(27-15-16-32(2)3)24-25(28-21)31-23(19-13-9-6-10-14-19)22(30-24)18-11-7-5-8-12-18/h5-14,17H,4,15-16H2,1-3H3,(H2,27,28,29,31,33)
• InChIKey: HHICWLZMNOCMIQ-UHFFFAOYSA-N
• SMILES: CCOC(=O)NC1=NC2=C(C(=C1)NCCN(C)C)N=C(C(=N2)C3=CC=CC=C3)C4=CC=CC=C4

UNC10217938A is a 3-deazapteridine analog with strong oligonucleotide enhancing effects. UNC10217938A enhances oligonucleotides effects by modulating their intracellular trafficking and release from endosomes. UNC10217938A also enhances the effects of antisense and siRNA oligonucleotides[1].
UNC10217938A 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 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 can substantially enhance effects of receptor targeted oligonucleotide conjugates. UNC10217938A also can enhance effects of uncharged morpholino oligonucleotides as well as negatively charged oligonucleotides[1].
Exposure of cells to UNC10217938A 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 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 (7.5 mg/kg; intravenous injection) produces distinct increases in EGFP fluorescence in liver, kidney and heart in EGFP654 mice[3].

Reference

[1]. Yang B, et al. High-throughput screening identifies small molecules that enhance the pharmacological effects of oligonucleotides. Nucleic Acids Res. 2015 Feb 27;43(4):1987-96.
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