Decitabine (NSC127716, 5AZA-CdR)

Decitabine (CAS No. 2353-33-5) is a nucleoside analog DNA methyltransferase (DNMT) inhibitor, with DNMT1 (a key enzyme maintaining DNA methylation) as its primary therapeutic target. At the cellular level, its IC₅₀ ranges from 10 to 100 nM; low doses (10~100 nM) mainly exert immunomodulatory effects, while high doses (≥1 μM) exhibit cytotoxicity. Clinically, it is indicated for the treatment of intermediate-risk to high-risk myelodysplastic syndromes (MDS) based on the International Prognostic Scoring System (IPSS). The intravenous dosage is 15 mg/m² once daily for 5 consecutive days as one cycle (repeated every 4 weeks). Additionally, it can be used at low doses in combination with anti-PD-1 antibodies for the treatment of relapsed/refractory classical Hodgkin lymphoma and advanced solid tumors (e.g., gastric cancer, esophageal cancer), which can reverse immunotherapy resistance with favorable safety profiles and no significant myelosuppression.

Decitabine increases the expression of γ-globulin through a post-transcriptional mechanism independent of DNA methylation, thereby enabling its incorporation into DNA and formation of irreversible covalent bonds with DNA methyltransferases at cytosine sites targeted for DNA methylation. It has been reported that decitabine possesses substantial efficacy in reactivating epigenetically silenced tumor suppressor genes. In colorectal cancer cell lines HCT116 and RKO, decitabine increases the ratio of acetylation of histone H3 lysine 9 (H3K9ac) to methylation on the unmethylated promoters of hMLH1 and MGMT, respectively. In T24 bladder cancer cells, decitabine can enhance the acetylation of histone H3 lysine 9 and methylation of histone H3 lysine 4 (H3K4me) on the unmethylated p14 promoter.

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