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December 8, 2025BloodOpen Access

EP31670, a dual-BET + p300 inhibitor, demonstrates pre-clinical efficacy, including in combination with JAK inhibition, in the hMPLW515L adoptive transfer model of myelofibrosis (MF)

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Authors

SWShishir WaghrayPBPrithviraj BoseLMLucia Masárová

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Overview

Pre-clinical trial shows EP31670 reduces fibrosis and inflammation in myelofibrosis models, suggesting a new treatment approach.

Key Points

  • This research investigates the pre-clinical efficacy of EP31670, a dual-BET and p300 inhibitor, in myelofibrosis models.
  • Utilized the hMPLW515L adoptive transfer model in lethally-irradiated BalbC mice.
  • Administered treatments: vehicle, EP31670, ruxolitinib, or combination therapy for three weeks.
  • Conducted flow cytometric and histopathologic analysis of BM and spleen samples.
  • Performed serum cytokine profiling using a 32-plex array kit.
  • EP31670 significantly reduced total white blood cell and platelet counts compared to other treatment arms.
  • Combination therapy with EP31670 and ruxolitinib showed distinct enhancements in efficacy.
  • Notable reductions in spleen volume were significant with combination therapy.
  • EP31670 improved bone marrow reticulin fibrosis and reduced megakaryocyte count, particularly in combination with ruxolitinib.

Cite This Study

Waghray et al. (2025) studied this question.

synapsesocial.com/papers/693624d74fa91c937236d137https://doi.org/10.1182/blood-2025-3759
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