5-クロロ-2-[((1S)-1-(5-フルオロピリミジン-2-イル)エチル)]アミノ-4-(5-メチル-1H-ピラゾール-3-イル-アミノ)ピリミジン

使用

AZD1480 has been used as an inhibitor of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in an in vitro cell model of upper gastrointestinal adenocarcinoma. It has also been used in combination with bortezomib to study tumor-associated macrophage-mediated survival of myeloma cells.

生物活性

AZD1480 is a novel small-molecule JAK inhibitor. It is able to block cell proliferation and induce apoptosis of myeloma cell lines. It can effectively inhibit tumor angiogenesis and metastasis mediated by STAT3 in stromal cells as well as tumor cells. AZD1480 has broad efficacy on a wider variety of myeloma cells, such as RPMI 8226, OPM-2, NCI-H929, Kms.18, MM1.S and IM-9, as well as primary myeloma cells. AZD1480 induces cell death of Kms.11 cells grown in the presence of HS-5 bone marrow (BM)-derived stromal cells and inhibits tumor growth in a Kms.11 xenograft mouse model, accompanied with inhibition of phospho-FGFR3, phospho-JAK2, phospho-STAT3 and Cyclin D2 levels. AZD1480 also demonstrates important Jak2 selectivity over Jak3, in particular at high ATP concentrations and marginal selectivity over Jak1 at Km ATP.

Biochem/physiol Actions

AZD1480 is an orally active, potent and selective inhibitor of Janus kinases JAK1 and JAK 2 with selectivity for JAK2 as evidenced by IC50 values of 1.3 nM for JAK1 and <0.4 nM for JAK2 in enzyme assays. AZD1480 inhibits endogenous as well as IL-6 induced STAT3 activation. AZD1480 reduces myeloid cell-mediated angiogenesis and metastasis. AZD1489 is an effective anticancer agent in bot adult and pediatric human tumors.