Protein Degradation and Inhibitors
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Latest in Protein Degradation and Inhibitors
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MKLN1 within the CTLH E3 ligase recognizes diverse substrates through multimodal engagement of acetylated, Arg, and C-degrons, revealing a versatile recognition mechanism.
- Open access
- 1 cites
Proteome-guided drug discovery identified linker modifications that reduce hepatotoxicity and improve safety of androgen receptor-targeting degraders for prostate cancer.
- Open access
Monovalent degraders can recruit two E3 ligases, DCAF16 and FBXO22, to degrade SMARCA2/4, with ligase dependency being chemically and genetically tunable.
- Open access
- 2 cites
TRI-611 is the first clinical-stage molecular glue degrader targeting ALK fusion proteins, achieving tumor regression in ALK-positive NSCLC models.
SAGA and ATAC co-activator complexes use different strategies, with distinct interactions and chromatin-reading capabilities, to regulate gene transcription in cancer cells.
- Open access
Venetoclax-controlled DROP-CAR T cells enable dose-dependent regulation of tumor targeting, reducing T cell binding to tumor cells in vitro and in vivo.
- Open access
- 2 cites
CLEO4-88 acts as a molecular glue with an EC50 of 12.5 nM to inhibit ACAA1 thiolase activity by inducing binding to GID4 in vitro and in cellulo.
- 1 cites
Ziftomenib combined with venetoclax and azacitidine achieves a 46% composite complete remission rate in relapsed/refractory NPM1-mutated AML patients at the 600 mg dose.
MutationProjector, a pre-trained genomic model, predicts therapeutic resistance and sensitivity across multiple cancer types with performance matching or exceeding state-of-the-art methods.
- Open access
Menin-MLL inhibitors increase JUND activity in MLL-rearranged leukemic cells, contributing to tumor growth and therapy resistance.
- Open access
A small molecule inhibitor, V20, was identified that modulates SAL enzyme activity, increasing PAP levels and stress tolerance in Arabidopsis thaliana.
- Open access
- 2 cites
Degrading NSD2 with a targeted ligand degrader reverses oncogenic chromatin changes and improves survival in t(4;14) multiple myeloma models.
Bitopic kinase inhibitors designed with optimized parameters can surpass existing drugs like ponatinib in potency and safety, especially against resistant ABL1 mutants.
- Open access
Off-target drug repurposing may provide a scalable therapeutic framework for rare cancers lacking canonical targets, with emerging evidence supporting its potential.
- Open access
HUWE1-HAPSTR1-USP7 complex amplifies ubiquitin chains on nuclear proteins, regulating stress-responsive degradation with a key role in neurodevelopmental disorders and cancer.
Heterobifunctional protein binders achieve cell-type-specific targeting with subnanomolar potency via FKBP12-dependent enrichment.
- Open access
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