FT895

FT895 is an inhibitor of histone deacetylase 11 (HDAC11; IC₅₀ = 3 nM).¹ It is selective for HDAC11 over HDAC1-7 (IC₅₀s = >10,000 nM for all), HDAC8 (IC₅₀ = 5,600 nM), and HDAC9-10 (IC₅₀s = >10,000 nM for both). FT895 induces cytotoxicity in Hs 53.T neurofibroma and S462.TY malignant peripheral nerve sheath tumor (MPNST) cells (IC₅₀s = 13.12 and 6.76 µM, respectively).² It increases the levels of reactive oxygen species (ROS) in S462.TY cells at 10 µM and reduces mitochondrial basal and maximal respiration at 10 and 20 µM in the same cells.³ FT895 (0.5 mg/kg) enhances the reduction in tumor size induced by cordycepin (Item No. 14426) in an S462.TY mouse xenograft model.² It also increases the production of nitric oxide (NO) in human monocyte-derived macrophages infected with heat-killed C. albicans. FT895 (50 mg/kg) reduces renal inflammation and fungal burden and increases survival in a mouse model of C. albicans infection.⁴

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1. Martin, M.W., Lee, J.Y., Lancia, D.R., Jr., et al. Discovery of novel N-hydroxy-2-arylisoindoline-4-carboxamides as potent and selective inhibitors of HDAC11. Bioorg. Med. Chem. Lett. 28(12), 2143-2147 (2018).

2. Huang, P.Y., Shih, I.A., Liao, Y.C., et al. A novel HDAC11 inhibitor potentiates the tumoricidal effects of cordycepin against malignant peripheral nerve sheath tumor through the Hippo signaling pathway. Am. J. Cancer Res. 12(2), 873-892 (2022).

3. Huang, P.Y., Shih, I.A., Liao, Y.C., et al. FT895 Impairs mitochondrial function in malignant peripheral nerve sheath tumor cells. Int. J. Mol. Sci. 25(1), 277 (2023).

4. Wu, H., Yin, X., Zhao, X., et al. HDAC11 negatively regulates antifungal immunity by inhibiting Nos2 expression via binding with transcriptional repressor STAT3. Redox Biol. 56, 102461 (2022).