AZD1480

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.

Reference

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[2].Michael Hedvat, Dennis Huszar, Andreas Herrmann, Joseph M. Gozgit, Anne Schroeder, Adam Sheehy, Ralf Buettner, David Proia, Claudia M. Kowolik, Hong Xin, Brian Armstrong, Geraldine Bebernitz, Shaobu Weng, Lin Wang, Minwei Ye, Kristen McEachern, Huawei Chen, Deborah Morosini, Kirsten Bell, Marat Alimzhanov, Stephanos Ioannidis, Patricia McCoon, Zhu A. Cao, Hua Yu, Richard Jove, Michael Zinda. The JAK2 Inhibitor AZD1480 Potently Blocks Stat3 Signaling and Oncogenesis in Solid Tumors. Cancer Cell. 2009; 16 (6): 487–497
[3].Hong Xin, Andreas Herrmann, Karen Reckamp, Wang Zhang, Sumanta Pal, Michael Hedvat, Chunyan Zhang, Wei Liang, Anna Scuto, Shaobu Weng, Deborah Morosini, Zhu A. Cao, Michael Zinda, Robert Figlin, Dennis Huszar, Richard Jove, Hua Yu. Antiangiogenic and Antimetastatic Activity of JAK Inhibitor AZD1480. Cancer Research. 2011;71: 6601-6610