OSMI-2

• CAT Number: I016836
• CAS Number: 2260542-60-5
• Molecular Formula: C26H25N3O7S2
• Molecular Weight: 555.62
• Purity: ≥95%
• Synonyms: methyl 2-[[(2R)-2-(2-methoxyphenyl)-2-[(2-oxo-1H-quinolin-6-yl)sulfonylamino]acetyl]-(thiophen-2-ylmethyl)amino]acetate
• InChI: InChI=1S/C26H25N3O7S2/c1-35-22-8-4-3-7-20(22)25(26(32)29(16-24(31)36-2)15-18-6-5-13-37-18)28-38(33,34)19-10-11-21-17(14-19)9-12-23(30)27-21/h3-14,25,28H,15-16H2,1-2H3,(H,27,30)/t25-/m1/s1
• InChIKey: ACLDUOSWRUIOSB-RUZDIDTESA-N
• SMILES: COC1=CC=CC=C1C(C(=O)N(CC2=CC=CS2)CC(=O)OC)NS(=O)(=O)C3=CC4=C(C=C3)NC(=O)C=C4

OSMI-2 (Compound 1b) is a cell-permeable O-linked N-acetylglucosamine transferase (OGT) inhibitor. Cells contain a large nuclear pool of partially spliced OGT transcript, and OSMI-2 increases detained intron splicing in cells[1].
OSMI-2 (Compound 1b; 20-50 μM; 4-24 hours; HCT116 cells) treatment reduces O-GlcNAc levels at short treatment times (<8h). However, O-GlcNAc levels begins to recover at longer treatment times with OSMI-2[1]. A decrease in HCF-1 cleavage products and the appearance of uncleaved HCF-1 in cells treated with OSMI-2 (Compound 1b) is observed. Because OGT knockdown is known to decrease cell proliferation, the effects of OSMI-2 on cell growth in culture over 96h is also monitored. Although there is no evidence of apoptosis, the reduced growth of cells over time is observed, consistent with the knockdown results[1]. A time course performed with 20 μM OSMI-2 (Compound 1b) shows reciprocal changes in the abundance of OGT and OGA, with a particularly large increase in OGT; this may explain the recovery in O-GlcNAc levels with OSMI-2. At 24h where O-GlcNAc levels fully recovered[1].

Reference

[1]. Martin SES, et al. Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors. J Am Chem Soc. 2018 Oct 24;140(42):13542-13545.
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