n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide and lestaurtinib
n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide has been researched along with lestaurtinib* in 2 studies
Reviews
1 review(s) available for n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide and lestaurtinib
Article | Year |
---|---|
Current outlook on molecular pathogenesis and treatment of myeloproliferative neoplasms.
Discovery of the JAK2 V617F mutation in the myeloproliferative neoplasms (MPNs) essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) has stimulated great interest in the underlying molecular mechanisms and treatment of these diseases. Along with acceleration of technologies, novel mutations in genes such as MPL, LNK, and CBL have been discovered that converge on the JAK-STAT pathway. Several additional novel mutations in genes involved in epigenetic regulation of the genome, including TET2, ASXL1, DNMT3A, and IDH1/2, have emerged, in addition to several mutations in cellular splicing machinery. While understanding of the pathogenetic mechanisms of these novel mutations in MPNs has improved, it is still lagging behind the pace of mutation discovery. Concurrent with molecular discoveries, especially with regard to JAK-STAT signaling, therapeutic development has accelerated in recent years. More than ten JAK kinase inhibitors have been advanced into clinical trials. Recently the first JAK2 inhibitor was approved for use in patients with PMF. Most JAK-targeting agents share similar characteristics with regard to clinical benefit, consisting of improvements in splenomegaly, constitutional symptoms, and cytopenias, for example. It remains to be determined if JAK2 inhibitors can considerably impact disease progression and bone marrow histologic features (e.g., fibrosis) or significantly impact the JAK2 allele burden. While JAK2 inhibitors appear to be promising in PV and ET, they need to be compared with standard therapies, such as hydroxyurea or interferon-based therapies. Future clinical development will focus on optimal combination partners and agents that target alternative mechanisms, deepen the response, and achieve molecular remissions. Topics: Adaptor Proteins, Signal Transducing; Alleles; Benzamides; Bridged-Ring Compounds; Carbazoles; Chromatin; Dioxygenases; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; DNA-Binding Proteins; Enhancer of Zeste Homolog 2 Protein; Epigenesis, Genetic; Furans; Gene Expression Regulation; Humans; Ikaros Transcription Factor; Intracellular Signaling Peptides and Proteins; Isocitrate Dehydrogenase; Janus Kinase 2; Mutation; Myeloproliferative Disorders; Nitriles; Polycomb Repressive Complex 2; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-cbl; Pyrazoles; Pyrimidines; Pyrrolidines; Receptors, Thrombopoietin; Repressor Proteins; Signal Transduction; Spliceosomes; Sulfonamides | 2012 |
Other Studies
1 other study(ies) available for n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide and lestaurtinib
Article | Year |
---|---|
JAK2 inhibitors and their impact in myeloproliferative neoplasms.
The BCR-ABL-negative myeloproliferative neoplasms (MPNs) include essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Historically, complex biochemical alterations defining these heterogeneously distinct malignancies have remained elusive and constrained available therapy options. The discovery of Janus kinase (JAK) mutations collectively present in BCR-ABL-negative MPNs has led to a resurgence of medical interest in JAK-STAT targeted treatment modalities, as well as provided a unique platform for inhibiting symptom-directing proinflammatory cytokines. INCB018424, CYT387, SB1518, and TG101348 are among the most propitious JAK2 inhibitors under investigation, providing substantial improvement in constitutional symptoms, transfusion-dependent cytopenias, and reduction in spleen size. Despite their attributes, evidence of complete or partial remission has yet to be observed with therapy. Many uncertainties surrounding the full clinical potential of JAK2 inhibitors persist. Treatment guidelines addressing optimal stages for drug implementation, ideal dosing parameters and criteria for medication continuation/withdrawal may effectively resolve these ongoing concerns and provide advancements in the morbidity and mortality of these multifaceted disease processes. Topics: Animals; Benzamides; Bridged-Ring Compounds; Carbazoles; Furans; Humans; Janus Kinase 2; Myeloproliferative Disorders; Nitriles; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Pyrrolidines; Sulfonamides | 2012 |