title: Pacritinib: a new agent for the management of myelofibrosis?
abstract: BACKGROUND
  Myelofibrosis (MF) is a clonal haematological disease associated with recurrent somatic gene mutations (JAK2V617F, MPL, CALR) and constitutive activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription pathway. MF is often characterised by debilitating symptoms and JAK inhibitors (JAKIs) have revolutionised available therapeutic options. Ruxolitinib, a JAK1 and 2 inhibitor, is the only currently approved agent. Several other JAKIs are undergoing evaluation in the clinical trial setting and Pacritinib , a novel JAK2 and FLT3 inhibitor, is at an advanced stage of investigation with recent completion of a Phase III trial and another ongoing.
  
  
  METHODS
  Within this article we focus on pacritinib, summarising the development, preclinical and up-to-date results from the Phase I - III trials. We present the most recent data on efficacy and safety and indirectly compare this novel JAKI with ruxolitinib.
  
  
  CONCLUSIONS
  The kinome array data for pacritinib suggests that it has a range of targets differing to those for ruxolitinib. Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients. It is also an attractive drug for potential combination studies due to its good tolerability.
authors.affiliation: a 1 Guy's and St. Thomas' NHS Foundation Trust, Department of Haematology , London, UK.
authors.forename: Yan
authors.initials: Y
authors.lastname: Beauverd
authors.affiliation: a 1 Guy's and St. Thomas' NHS Foundation Trust, Department of Haematology , London, UK.|b 2 King's College Hospital NHS Foundation Trust, Department of Haematological Medicine , London, UK.
authors.forename: Donal P
authors.initials: DP
authors.lastname: McLornan
authors.affiliation: c 3 Guy's and St. Thomas' NHS Foundation Trust, Department of Haematology , London, UK Claire.Harrison@gstt.nhs.uk.
authors.forename: Claire N
authors.initials: CN
authors.lastname: Harrison
mesh_terms: D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy*; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D013163:Splenomegaly / Q000188:drug therapy
chemical_list: C561234:11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; D001952:Bridged-Ring Compounds; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: Janus kinase inhibitors; myelofibrosis; myeloproliferative disease; pacritinib; ruxolitinib; treatment