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December 8, 2025Blood

Discovery of drug combinations with momelotinib to improve myelofibrosis outcomes

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Authors

SOShane W. O’BrienALAshley LentoAHAllison Hartman

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Overview

Drug combinations with momelotinib improve anemia and splenomegaly in myelofibrosis, suggesting potential therapeutic benefits.

Key Points

  • The aim is to discover drug combinations that enhance the clinical outcomes of momelotinib in myelofibrosis.
  • Conducted two high-throughput drug screens using over 600 small molecules in isogenic cell lines with JAK-STAT pathway mutations.
  • The VAF screen focused on inhibitors of pathways parallel to JAK-STAT signaling.
  • The hepcidin screen identified inhibitors that suppressed the expression of a hepcidin transgene.
  • Identified several drug combinations that reduce viability of malignant cells in myelofibrosis.
  • Combination of momelotinib with selinexor showed promise in killing malignant cells and suppressing hepcidin expression.
  • Discoveries provide a scientific basis for optimizing combination regimens to improve patient outcomes in myelofibrosis.

Cite This Study

O’Brien et al. (2025) studied this question.

synapsesocial.com/papers/69362f6c4fa91c937236dfcdhttps://doi.org/10.1182/blood-2025-7279
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Also Consider

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

  1. 1Abstract 5870: Momelotinib: Unique polypharmacology and novel combination strategies for myelofibrosis and beyond2026
  2. 2Momelotinib's unique polypharmacology supports indication expansion beyond myelofibrosis2025
  3. 3Momelotinib in myelofibrosis: JAK1/2 inhibitor with a role in treating and understanding the anemia2016 · 16 citations
  4. 4Efficacy of Momelotinib in Myelofibrosis Patients: Results From a Multicenter Study2025 · 2 citations
  5. 5Efficacy and Safety of Momelotinib in Myelofibrosis: A Systematic Review and Meta-Analysis With a Focus on Anemia Outcomes.2025 · 2 citations