UM626

UM626 is an orally bioavailable, small-molecule molecular glue degrader developed by RejuvenRx for the treatment of myeloproliferative neoplasms (MPNs), acute myeloid leukemia (AML), and for thymic rejuvenation and immune reconstitution. UM626 acts by recruiting the E3 ligase Kelch repeat and BTB domain-containing protein 4 (KBTBD4) to induce the selective degradation of the CoREST complex, which includes REST corepressor 1 (RCOR1), REST corepressor 3 (RCOR3), lysine-specific histone demethylase 1A (LSD1), and histone deacetylases 1 and 2 (HDAC1/2). By dismantling this central epigenetic regulator, UM626 rejuvenates the blood system, reprograms primitive myeloid progenitors, and restores thymic function to re-establish healthy T-cell production. The drug is currently in preclinical development (lead optimization) for oncology indications and exploratory Phase 0 development for thymic rejuvenation and immune reconstitution.