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December 8, 2025BloodOpen Access

Discovery of JAK2V617F mutant specific allosteric inhibitors for the treatment of myeloproliferative neoplasms

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Authors

APAnil K. PadyanaTMTrisha MoroJLJoseph LaPointe

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Overview

Discovery of potent allosteric inhibitors selectively reducing JAK2V617F signaling in hematopoietic cancer cells, indicating new therapies for myeloproliferative neoplasms.

Key Points

  • Allosteric inhibitors effectively suppress JAK2V617F driven signaling in hematopoietic cancer cell lines.
  • Selected compounds showed robust target engagement and favorable pharmacokinetic profiles in animal models.
  • Therapies maintain normal signaling in wild-type JAK2, reducing treatment limiting adverse events.
  • Early assessments confirm significance in developing mutant-selective therapies for myeloproliferative neoplasms.

Cite This Study

Padyana et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd54https://doi.org/10.1182/blood-2025-1977
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Also Consider

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

  1. 1Identification of novel, potent, and selective JAK2V617F inhibitors2025 · 1 citations
  2. 2Preclinical characterization of a novel, wild-type-sparing, JAK2 V617F mutant-selective inhibitor2025
  3. 3Selective ASO-based JAK2 inhibitor for the treatment of hematological malignancies with JAK2 V617F mutation burden2025
  4. 4AJ1-11095, a potent and highly selective type-II JAK2 inhibitor, shows enhanced therapeutic efficacy as compared with type-I JAK2 inhibitor ruxolitinib in models of myeloproliferative neoplasms (MPNs)2025 · 1 citations
  5. 5Discovery of Highly Selective and Potent Macrocyclic JAK2 Inhibitors for the Treatment of MPNs2025 · 1 citations