Tucidinostat (Chidamide)

Description

Chidamide is an inhibitor of histone deacetylases (HDACs; IC₅₀s = 0.095, 0.160, 0.067, 0.733, 0.078, and 0.432 μM for HDAC1-3, 8, 10, and 11, respectively). It is selective for these HDACs over HDAC4-7 and 9 (IC₅₀s = >30 μM for all). Chidamide also inhibits nicotinamide phosphoribosyltransferase (Nampt; IC₅₀ = 2.1 μM). It inhibits cell growth in a panel of 18 cancer cell lines (GI₅₀s = 0.4-40 μM) but has no effect on the growth of non-cancerous CCC-HEK human fetal kidney or CCC-HEL human liver cells (GI₅₀s = >100 μM). In vivo, tucidinostat (12.5, 25, and 50 mg/kg) reduces tumor growth in HCT-8, A549, BEL-7402, and MCF-7 mouse xenograft models.

Uses

Chidamide is a newly designed histone deacetylase inhibitor that induces an antitumor effect in various cancer by increasing the acetylation levels of histone H3 and decrease histone deacetylase (HDAC) activity, induces apoptosis. Also, it is a potential utility of Chidamide for the treatment of Myelodysplastic syndromes.

Definition

ChEBI: Chidamide is a member of benzamides.

in vivo

IC 50

HDAC3: 67 nM (IC₅₀); HDAC10: 78 nM (IC₅₀); HDAC1: 95 nM (IC₅₀); HDAC2: 160 nM (IC₅₀); HDAC11: 432 nM (IC₅₀); HDAC8: 733 nM (IC₅₀)

References

[1] ZHI-QIANG NING. Chidamide (CS055/HBI-8000): a new histone deacetylase inhibitor of the benzamide class with antitumor activity and the ability to enhance immune cell-mediated tumor cell cytotoxicity.[J]. Cancer Chemotherapy and Pharmacology, 2012, 69 4: 901-909. DOI: 10.1007/s00280-011-1766-x
[2] YING WU. Nicotinamide Phosphoribosyltransferase (NAMPT) Is a New Target of Antitumor Agent Chidamide[J]. ACS Medicinal Chemistry Letters, 2019, 11 1: 40-44. DOI: 10.1021/acsmedchemlett.9b00407