Researchers from Incyte Corp. and collaborators presented the preclinical profile of INCB-160058, an ATP-competitive small-molecule inhibitor of the JAK2 V617F mutant sparing its wild-type (WT) form, designed for the treatment of JAC2 V617F mutation-positive myeloproliferative neoplasms with potential as a first-in-class JAK2 V617-inhibiting drug.
Among the acquired mutations in the calreticulin (CALR) gene, both 52 bp deletion (del52) and 5 bp insertion (ins5) are among the most frequent and are linked to two different types of myeloproliferative neoplasms (MPNs).
Myeloproliferative neoplasms (MPNs) can only be cured, to date, using allogeneic stem cell transplantation which, in turn, only works for up to 20% of patients. As calreticulin (CALR) frameshift mutations are the second most common cause of MPNs, targeting this endoplasmic reticulum resident protein is one of the strategies emerging at the forefront of hematological malignancies research.
Myeloproliferative neoplasms (MPNs) are a group of disorders of which the main hallmarks are bone marrow fibrosis and atypical megakaryocytes (MK) accumulation. Both Rho kinase (ROCK) and Aurora kinase (ARK) pathways are involved in correct MK maturation.
Type I JAK2 inhibitors improve symptoms and outcomes of patients with myeloproliferative neoplasms (MPNs), but mutant allele JAK2 VF remains unchanged with this therapy. Type II JAK2 inhibitors bind the inactive conformation of the kinase domain and reduce the fraction of JAK2 VF mutant allele in vivo, suggesting an improved approach for JAK2 inhibition. Ajax Pharmaceuticals Inc. presented preclinical data on the type II JAK2 inhibitor AJ1-10502 for the treatment of MPNs.
DUBLIN – Fans of “His Dark Materials” and the “Book of Dust,” Philip Pullman’s series of fantasy novels set in Oxford, U.K. and more remote corners of the earth, are familiar with alethiometers. In the hands of a highly select number of characters, these complex, compass-like devices can interrogate a mysterious substance called “dust” – an elementary particle associated with consciousness – and provide trusted answers to the most crucial questions.
