AZD1208 | pan-PIM kinase inhibitor

AZD1208 (1204144-28-4) is a highly selective and potent pan-PIM kinase inhibitor (IC₅₀ = 3 nM PIM1; 150 nM PIM2; 9 nM PIM3).¹ Displayed efficacy in models of acute myeloid leukemia², prostate cancer³, and triple-negative breast cancer⁴.  Combination treatment of AZD1208 and imatinib eliminated chronic myelogenous leukemia stem cells in cell culture and a patient-derived mouse xenograft model.⁵ It improved immunotherapeutic antitumor T-cell response⁶ and disrupted the myeloid cell-mediated immunosuppressive tumor microenvironment increasing T-cell-mediated antitumor immunity.

References/Citations:

1. Dakin et al. (2012), Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases; Bioorg. Med. Chem. Lett. 22 4599
2. Keeton et al. (2014), AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia; Blood 123 905
3. Kirschner et al. (2014), PIK kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer; J. Natl. Cancer Inst. 107 dju407
4. Braso-Maristany et al. (2016), PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer; Nat. Med. 22 1303
5. Ma et al. (2019), Prosurvival kinase PIM2 is a therapeutic target for eradication of chronic myeloid leukemia stem cells; Proc.Natl. Acad. Sci. USA 116 10482
6. Chatterjee et al. (2019), Targeting PIM Kinase with PD1 Inhibition Improves Immunotherapeutic Antitumor T-cell Response; Clin. Cancer Res. 25 1036
7. Xin et al. (2021), Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer; Cancer Immunol. Res. 9 454