Ruxolitinib phosphate

Details:

Physical and Chemical Properties    
Ruxolitinib, (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3- cyclopentylpropanenitrile phosphate, has a molecular weight of 404.36 kDa. Ruxolitinib is soluble in aqueous solutions at pH 1-8. Ruxolitinib tablets are stable at 20-25°C and tolerate brief exposures to temperatures outside this range, if they stay within 15-30°C.

Approval for Use    
Ruxolitinib is an oral inhibitor of JAK1 and JAK2, which is approved for the treatment of myeloproliferative neoplasm-associated myelofibrosis, further myeloproliferative neoplasms, polycythemia vera and refractory cancer. In the USA, Canada and EU, ruxolitinib is approved for the treatment of patients with intermediate or high-risk PMF, post-PV MF or post-ET MF. In addition, ruxolitinib recently has been approved for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea, based on the results of Phase II and III clinical studies. To date, ruxolitinib has been approved for indications in MF in 83 countries.

Side Effects    
Common side effects of ruxolitinib treatment include anaemia and thrombocytopenia. The decline of circulating erythrocytes following ruxolitinib treatment could result in part from stimulation of eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the cell surface. Cellular mechanisms involved in the execution of eryptosis include oxidative stress, Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), ceramide, decline of cytosolic ATP, caspases, stimulated activity of casein kinase 1α, Janus-activated kinase JAK3, protein kinase C, and p38 kinase, as well as impaired activity of AMP activated kinase AMPK, cGMP-dependent protein kinase, PAK2 kinase and sorafenib/sunitinib sensitive kinases.

Uses    The phosphate salt of Ruxolitinib (R702000). Ruxolitinib is a selective Janus tyrosine kinase (JAK1 and JAK2) inhibitor used in the treatment of myeloproliferative neoplasms and psoriasis.
Definition    ChEBI: A phosphate salt obtained by reaction ruxolitinib with one equivalent of phosphoric acid. Used for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essent al thrombocythemia myelofibrosis.
Clinical Use    Ruxolitinib phosphate is a potent, selective, ATP competitive inhibitor of tyrosine-protein kinases JAK1 and JAK2 which acts by attenuating cytokine signaling and promotes apoptosis. Ruxolitinib was discovered and developed by Incyte, is marketed under the brand name Jakafi,and is approved for the treatment of patients with myelofibrosis (MF), including primary MF, post-polycythemia vera MP, and post-essential thrombocythemia MF. Ruxolitinib is also undergoing clinical evaluation against a wide variety of cancer indications including metastatic prostate cancer, pancreatic cancer, multiple myeloma, leukemia, non-Hodgkin lymphoma, and breast cancer. Additionally, ruxolitinib is being evaluated for the treatment of psoriasis and thrombocytopenia.