ルキソリチニブ 化學特性,用途語,生産方法
効能
抗悪性腫瘍薬, ヤヌスキナーゼ (JAK) 阻害薬
説明
In November 2011, the U.S. FDA approved ruxolitinib (INCB018424)
for the treatment of patients with intermediate or high-risk myelofibrosis.
Ruxolitinib is
an ATP-competitive inhibitor of JAK1 and JAK2 (IC
50's of 3.3±1.2 nM
and 2.8±1.2 nM, respectively) and inhibition occurs regardless of the
JAK2V617F mutational status. Ruxolitinib is a moderately potent inhibitor
of the related JAK, TYK2 (IC
50=19±3.2 nM) but is selective versus
JAK3 (IC
50=428±243 nM). It was also selective versus a panel of 26 other
kinases at concentrations approximately 100-fold the IC
50 of JAK1 and
JAK2. Inhibition of JAK1 and JAK2 downregulates the JAK-signal transducer
and activator of transcription (STAT) pathway, inhibiting
myeloproliferation, inducing apoptosis, and reducing numerous cytokine
plasma levels.
特性
Class: non-receptor tyrosine kinase
Treatment: MF, PV, cGVHD
Oral bioavailability >95%
Elimination half-life = 3 h
Protein binding = 97%
使用
Ruxolitinib is a selective Janus tyrosine kinase (JAK1 and JAK2) inhibitor used in the treatment of myeloproliferative neoplasms and psoriasis.
適応癥
The JAK family includes four isoforms, JAK1, JAK2, JAK3, and tyrosine kinase (TYK2). Ruxolitinib (Jakafi(R), Incyte Corp.) was the first approved JAK inhibitor, which inhibits both JAK1 and JAK2, used for the treatment of different types of myelofibrosis. Tofacitinib (Xeljanz(R), Pfizer) was approved by FDA as a JAK3-selective inhibitor for the treatment of rheumatoid arthritis and is one of the only two FDA-approved kinase inhibitors for non-oncological indications.
定義
ChEBI: A pyrazole substituted at position 1 by a 2-cyano-1-cyclopentylethyl group and at position 3 by a pyrrolo[2,3-d]pyrimidin-4-yl group. Used as the phosphate salt for the treatment of patients with intermediate or high-risk myelofibrosis, includ
ng primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
ルキソリチニブ 上流と下流の製品情報
原材料
準備製品