Rbin-2

Rbin-2 is a small molecule inhibitor of midasin (MDN1), a massive AAA+ ATPase essential for ribosome biogenesis, specifically the maturation of the 60S ribosomal subunit. Identified as an analog of Rbin-1, Rbin-2 binds to the AAA+ ring of midasin and inhibits its function. In the context of oncology research, particularly at Florida A&M University, Rbin-2 has demonstrated the ability to inhibit the growth and invasion of endocrine-resistant breast cancer cells, including those harboring ESR1 mutations (e.g., Y537S, D538G). It disrupts the SUMO2/3–SENP3–MDN1 regulatory axis, leading to impaired mammosphere stability and reduced expression of cancer stem cell markers like OCT4 and SOX2. Rbin-2 also shows synergistic activity when combined with the selective estrogen receptor degrader (SERD) elacestrant.