2. Academic Validation
  3. Discovery of novel itaconimide-based derivatives as potent HDAC inhibitors for the efficient treatment of prostate cancer

Discovery of novel itaconimide-based derivatives as potent HDAC inhibitors for the efficient treatment of prostate cancer

  • Eur J Med Chem. 2024 Apr 5:269:116315. doi: 10.1016/j.ejmech.2024.116315.
Qihe Jiang 1,  Yujiang Tang 1,  Qinglan Hu 1,  Bichuan Wang 1,  Xiuqin Ruan 1,  Qingfa Zhou 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Department of Organic Chemistry, China Pharmaceutical University, Nanjing, 210009, China.
  • 2 State Key Laboratory of Natural Medicines, Department of Organic Chemistry, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: [email protected].
PMID: 38503167 DOI: 10.1016/j.ejmech.2024.116315
Abstract

Histone deacetylases (HDACs) are a family of enzymes that play important roles in the development and progression of cancers. Inhibition of HDACs has been widely studied as a therapeutic strategy in the development of Anticancer drugs. However, developing HDAC inhibitors that are effective for solid tumors remains a great challenge. In this work, we designed and synthesized a series of itaconimide-based derivatives as potent HDAC inhibitors. Among them, compound 17q exhibited potent inhibition of HDAC1/2/3/6, with good antiproliferative activity in vitro and an excellent pharmacokinetic profile. Compound 17q significantly inhibited tumor growth in a DU145 xenograft tumor model and showed no obvious toxicity. Moreover, when 17q was combined with other prostate Cancer therapeutics, outstanding synergistic effects were observed and the toxic side effects of DTX were reduced. Overall, based on the data, these inhibitors may offer promising new targeted therapies for prostate Cancer.

Keywords

Antiproliferative; HDAC; Itaconimide; Prostate cancer; Treatment.

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