MRT-31619

MRT-31619 is a selective CRBN Molecular glue degrader, with an IC₅₀ of 14 nM and an EC 50 of 72 nM. MRT-31619 triggers ubiquitination and proteasomal degradation of CRBN. MRT-31619 serves as a chemical knockout tool for CRBN depletion to evaluate the dependence of other molecular glues on CRBN. MRT-31619 is applicable to the research of CRBN -related disease models ^{[1] [2]}.

In Vitro, MRT-31619 (1-10 μM; 1-24 h) potently and selectively degrades CRBN in Jurkat cells: this effect occurs after treatment at 1 μM for 1 h, 3 h and 24 h, as well as after treatment at 10 μM for 24 h, without affecting the level of DDB1^[1]. Incubation of purified recombinant CRBN-DDB1 complex with MRT-31619 (10 μM; 60 min) induces the formation of CRBN-DDB1 dimeric complex^[1]. MRT-31619 induces the formation of CRBN ternary complex, with an EC50 of 72 nM as determined by FIDA assay using purified recombinant CRBN-DDB1 complex^[1]. MRT-31619 efficiently and selectively degrades CRBN via a self-targeting mechanism involving CRBN homodimerization, with a CRBN-binding IC₅₀ of 14 nM and a complex-formation EC50 of 72 nM in Jurkat cells^[2].

References:
[1]. Langousis G, et al. A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation. Nature communications. 2025 Nov 19;16(1):10157.
[2]. Won H J, et al. Synthetic and Medicinal Chemistry Perspectives on Cereblon‐Binding Molecular Glue Degraders: Recent Advances and Emerging Trends[J]. European Journal of Organic Chemistry, 2026, 29(17): e202501208.