Oxamflatin is a potent histone deacetylase inhibitor with IC50 value of 15.7 nM [1].
Histone deacetylases (HADC) are a series of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone and make the histones to wrap the DNA more tightly, which prevent transcription.
Oxamflatin is a potent histone deacetylase inhibitor and a novel antitumor compound. In mouse and human tumor cell lines, such as P388, Lewis, Lu-99, HT-29 and HeLa cells, Oxamflatin exhibited antiproliferative activity. In HeLa cells, Oxamflatin changed cell morphology, and significantly reduced the number of the cells in S phase and increased the number of cells in G0/G1 phase [1]. In the HIV-1 latently infected Jurkat T cell line, Oxam?atin increased the acetylation level of histone H3 and histone H4 at the nucleosome 1(nuc-1) site of the HIV-1 LTR and activated HIV-1 gene expression by 2-17 fold, suggesting that Oxam?atin has potential as drug candidates as antilatency therapies [2]. In OVCAR-5 and SKOV-3 ovarian cancer cell lines, oxamflatin decreased cell viability and significantly inhibited DNA synthesis and cell proliferation. Also, oxamflatin reduced the expression of c-Myc, CDK4 and E2F1, and the phosphorylation level of Rb protein, but upregulated p21 [3].
In mice transplanted with B16 murine melanoma, Oxamflatin (20 mg/kg) injected intraperitoneally six times on day 1, 3, 5, 7, 9 and 11 significantly increased the days of survival [1].
References:
[1].Kim YB, Lee KH, Sugita K, et al. Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase. Oncogene. 1999 Apr 15;18(15):2461-70.
[2].Yin H, Zhang Y, Zhou X, et al. Histonedeacetylase inhibitor Oxamflatin increase HIV-1 transcription by inducing histone modification in latently infected cells. Mol Biol Rep. 2011 Nov;38(8):5071-8.
[3].Wang YL, Liui HL, Fu RG, et al. HDAC Inhibitor Oxamflatin Induces Morphological Changes and has Strong Cytostatic Effects in Ovarian Cancer Cell Lines. Curr Mol Med. 2016;16(3):232-42.