Background:

Rbin-1 is an eukaryotic ribosome assembly inhibitor.

All cellular proteins are synthesized by ribosomes, whose biogenesis is a complex multi-step process quickly completed in eukaryotes. Several chemical inhibitors of ribosome function are available, however, potent validated chemical probes are still lacking to analyze the dynamics of eukaryotic ribosome assembly.

In vitro: In the mode of action study of Rbin-1, the MDR-sup fission yeast cells was chemically mutagenized and the resistant clones that can grow in the presence of Rbin-1 were isolated. Results found that each of the 13 Rbin-1 resistant clones had one of five different point mutations in the mdn1 gene. It was further confirmed that, using overexpression on plasmids in MDR-sup cells and by replacement of endogenous mdn1 in wild-type cells, all the identified mutations were enough to confer resistance to Rbin-1. In addition, Rbin-1 at 1 μM was able to inhibit the ATPase activity by around 40%. Moreover, the nuclear export of the pre-40S subunits that were tracked using two different reporters, Rps3- GFP and Rps2-GFP, could not be blocked in Rbin-1-treated cells, suggesting that Mdn1 had specific roles in pre-60S ribosome assembly [1].

In vivo: So far, there is no animal in vivo data reported.

Clinical trial: Up to now, Rbin-1 is still in the preclinical development stage.

Reference:
[1] Kawashima SA, Chen Z, Aoi Y, Patgiri A, Kobayashi Y, Nurse P, Kapoor TM.  Potent, Reversible, and Specific Chemical Inhibitors of Eukaryotic Ribosome Biogenesis. Cell. 2016 Oct 6;167(2):512-524.e14.