JNJ-26481585 (hydrochloride)

JNJ-26481585 is a histone deacetylase (HDAC) inhibitor.¹ It inhibits class I (IC₅₀s = 0.11, 0.33, 4.86, and 4.26 nM for HDAC1, -2, -3, and -8, respectively), class IIa (IC₅₀s = 0.64, 3.69, 119, and 32.1 nM for HDAC4, -5, 7-, and -9, respectively), and class IIb HDACs (IC₅₀s = 76.8 and 0.46 nM for HDAC6 and HDAC10, respectively), as well as HDAC11 (IC₅₀ = 0.37 nM), the class IV HDAC. JNJ-26481585 (200 nM) induces apoptosis, pyroptosis, and ferroptosis in CAL-27 and Tca8113 tongue squamous cell carcinoma cells.² It also induces histone H3 acetylation in tumor tissue in vivo and completely inhibits tumor growth in HCT116 Ras mutant and C170HM2 mouse xenograft models when administered at a dose of 10 mg/kg once per day.¹

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1. Arts, J., King, P., Mariën, A., et al. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin. Cancer. Res 15(22), 6841-6851 (2009).

2. Wang, X., Liu, K., Gong, H., et al. Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis. Toxicol. Appl. Pharmacol. 410, 115363 (2021).