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December 8, 2025BloodOpen Access

Amx-883, a potent and selective degrader of BRD9 drives differentiation in acute myeloid leukaemia and shows synergistic efficacy in combination with venetoclax In Vivo and prevents the emergence of resistance to venetoclax in vitro.

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Authors

LMLouise K. ModisRHRebecca HarrisAAAleksandra Azevedo

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Overview

Preclinical analysis demonstrates amx-883 enhances differentiation and reduces leukemic burden in acute myeloid leukaemia, indicating synergy with venetoclax.

Key Points

  • Differentiation was significantly enhanced in acute myeloid leukaemia cells treated with AMX-883, leading to reduced leukemic cell survival.
  • For total leukemic burden, treating animal models with AMX-883 showed marked tumor reduction compared to vehicle-treated controls.
  • Assessment involved a novel degrader AMX-883, demonstrating robust degradation of BRD9 while preserving normal cell viability.
  • Significantly, combining AMX-883 and venetoclax revealed synergistic effects against leukemic cell lines, preventing resistance development.

Cite This Study

Modis et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dcd6https://doi.org/10.1182/blood-2025-1489
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Investigating KAT2A protac therapy for targeting leukemic blast differentiation in acute myeloid leukaemia.2025
  2. 2Inhibition of <scp>CDK</scp>9 enhances <scp>AML</scp> cell death induced by combined venetoclax and azacitidine2025
  3. 3EB2023 primes mitochondria for BCL2 dependence and induces pyroptotic cell death via AMPK signaling and the unfolded protein response2025
  4. 4Targeting BRD9 in KMT2A-rearranged Acute Myeloid Leukemia to circumvent MEN1 inhibitor resistance2025
  5. 5Single-cell insights into acute myeloid leukemia treated with venetoclax-based therapy2025