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December 8, 2025BloodOpen Access

Proteolysis-targeting chimera (PROTAC) targeting bruton tyrosine kinase (BTK) degradation for cancer therapy in mantle cell lymphoma

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Authors

XWXianhuo WangHZHuilai Zhang

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Overview

C23 demonstrates growth inhibition and apoptosis in mantle cell lymphoma, suggesting potential against acquired resistance.

Key Points

  • Evaluate the effectiveness of BTK-PROTAC C23 in degrading BTK and inhibiting mantle cell lymphoma cells.
  • Designed and synthesized several BTK-PROTACs.
  • Screened BTK-PROTACs using in vitro assays and a mouse model.
  • Analyzed effects on gene expression and BCR signaling using RNA sequencing.
  • C23 showed the strongest ability to induce BTK degradation and inhibit MCL cell proliferation.
  • C23 activated the ubiquitin-proteasome pathway, leading to apoptosis.
  • C23 inhibited growth of BTK variant cells resistant to BTK inhibitors in xenograft models.

Cite This Study

Wang et al. (2025) studied this question.

synapsesocial.com/papers/69362f5d4fa91c937236dc2chttps://doi.org/10.1182/blood-2025-7852
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