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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 findings reveal EP31670 reduces inflammatory cytokines and improves outcomes in myelofibrosis, highlighting its potential as a combination therapy.

Key Points

  • This research investigates the therapeutic efficacy of EP31670, a dual BET and p300 inhibitor, in myelofibrosis models.
  • Utilized the hMPLW515L adoptive transfer model with lethally-irradiated BalbC mice.
  • Mice were treated with vehicle, EP31670, ruxolitinib, or combination therapy.
  • Monitored treatment effects on spleen volume, blood cell counts, and cytokine profiles.
  • EP31670 significantly reduced total white blood cell and platelet counts compared to controls.
  • Combination therapy demonstrated enhanced spleen volume reduction.
  • Substantial reductions in inflammatory cytokines were observed with EP31670 treatment.

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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Also Consider

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

  1. 1Momelotinib inhibition of JAK/STAT in a mouse JAKV617F myelofibrosis model showed concurrent activation of p-ERK and p-AKT which was reversed by combination therapy using LP-182, a novel MEK/PI3K/mTOR inhibitor2025
  2. 2Direct small molecule inhibition of RAS enhances JAK2 inhibitor therapy in preclinical models of myeloproliferative neoplasms2025
  3. 3Disrupting a new NFkB-IL-6-JAK2-STAT cascade with novel NFkB inhibitors reduces primary myelofibrosis growth2025
  4. 4Magnetic resonance imaging maps spatiotemporal changes in bone marrow composition of murine JAKV617F models of myelofibrosis during progression and therapy2025
  5. 5A phase I study of the combination of ruxolitinib and the ERK1/2 inhibitor ulixertinib in previously treated myelofibrosis patients.2025