Bcr-Abl Degrader

MRLB-223 is a preferential HDAC1 and HDAC2 inhibitor with activity against tumor cells.MRLB-223 induces histone hyperacetylation, intrinsic apoptotic pathway activation, tumor cell apoptosis, Hsp90 hyperacetylation, and caspase-dependent Bcr-Abl degradation.MRLB-223 mediates p53-independent tumor cell death, with activity suppressed by Bcl-2 overexpression, and kills Bcr-Abl-expressing myeloid cells.MRLB-223 exerts effects in mice bearing Eμ-myc lymphomas.MRLB-223 can be used for the research of Eμ-myc lymphoma.

ML 2-23 is a PROTAC degrader that recruits RNF114 to target BCR-ABL/c-ABL for degradation. ML 2-23 promotes proteasome-dependent degradation of the target protein and inhibits phosphorylation of downstream CRKL. At concentrations used for BCR-ABL degradation, ML 2-23 only causes slight impairment to the viability of cancer cells. ML 2-23 can be used in the research of chronic myeloid leukemia.

Phe-PEG1-Dasa is a BCR-ABL PROTAC degrader, with its DC₅₀ being 1.56 nM. Phe-PEG1-Dasa uses a single amino acid (Phe) as the E3 ligand and employs the N-end rule pathway to induce the degradation of the target protein, significantly reducing the molecular size, thus being called a mini-PROTAC. Phe-PEG1-Dasa significantly inhibits the proliferation of K562 cells. Phe-PEG1-Dasa can be used for the study of leukemia.