HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Selective Janus associated kinase 1 inhibition as a therapeutic target in myelofibrosis.

Abstract
Hyperactive Janus associated kinase-signal transducers and activators of transcription (JAK-STAT) signaling has been shown to be integral to the pathogenesis of myelofibrosis (MF) regardless of the driver mutational status (JAK2V617F, JAK2 exon 12, MPL515L/K, CALR). Targeting of the JAK-STAT pathway has been the intense focus of therapeutic development and led to the approval of the JAK1/2 inhibitor, ruxolitinib. Despite the clear clinical success of ruxolitinib, dose limiting thrombocytopenia, treatment associated anemia and failure to effectively achieve bone marrow pathologic, cytogenetic and molecular remission remain shortcomings. JAK1 inhibition leads to depression in inflammatory cytokine expression associated with MF-related constitutional symptoms. The selective targeting of JAK1 may provide an opportunity to alleviate MF-related symptoms without anti-JAK2 therapy-related myelosuppression. Additionally, a JAK1 inhibitor may serve as an ideal candidate partner for combination therapeutic approaches in the treatment of MF. Current evaluation of selective JAK1 inhibition in MF will further clarify the relative contribution of aberrant JAK1 signaling to the pathogenesis of MF.
AuthorsJohn Mascarenhas
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 56 Issue 9 Pg. 2493-7 ( 2015) ISSN: 1029-2403 [Electronic] United States
PMID25586607 (Publication Type: Journal Article, Review)
Chemical References
  • Cytokines
  • Inflammation Mediators
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Janus Kinase 1
Topics
  • Cytokines (metabolism)
  • Humans
  • Inflammation Mediators (metabolism)
  • Janus Kinase 1 (antagonists & inhibitors, metabolism)
  • Nitriles
  • Primary Myelofibrosis (drug therapy, metabolism)
  • Protein Kinase Inhibitors (therapeutic use)
  • Pyrazoles (therapeutic use)
  • Pyrimidines
  • Signal Transduction (drug effects)
  • Treatment Outcome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: