Argonaute-2 Inhibitor, BCI-137

A cell-permeable dioxotetrahydroquinoxaline compound that mimics uridine monophosphate for affinity interaction at the Argonaute-2 (Ago2) Mid domain (K_D = 126 µM) and effectively inhibits Ago2 cellular miRNA loading in acute promyelocytic leukemia (APL) NB4 cultures (% inhibition by RIP = 79%/miR-107, 73%/let-7a, 73%/miR-223, 68%/miR-26a, 53%/miR-60a; 100 nM for 48 h) without affecting cellular Ago2 stability. Consistent with the involvement of Ago2 in heterochromatic miR-155HG silencing, BCI-137 is reported to decrease miR-155HG promoter region-associated Ago2 with a concomitant acetylation induction of the promoter region-associated histone H4 (70% reduced Ago2 association and 300% enhanced H4 acetylation, respectively, by ChIP; 10 µM). Likewise, Ago2 inhibition by BCI-137 is shown to boost Retinoic Acid-(RA, Cat. no. 554720) induced NB4 granulocyte differentiation as a result of greatly upregulated expression of the differentiation-related miRNAs (140% and 255% increased miR-26a and miR-223 level, respectively, compared to 100 nM RA stimulation alone for 96 h) without affecting NB4 proliferation or viability (up to 10 µM and 96 h with or without 100 nM RA stimulation).

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Cell permeable: yes

Primary Target
Argonaute-2

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Masciarelli, S., et al. 2014. ACS Chem. Biol.9, 1674.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)