See the DrugPatentWatch profile for azacitidine

Azacitidine is a drug that has been shown to have an impact on abnormal histones in graft-versus-host disease (GVHD) [1]. GVHD is a common complication that can occur after a stem cell or bone marrow transplant, where the donated immune cells attack the patient's body [2].

Azacitidine works by inhibiting DNA methyltransferase, which leads to hypomethylation of DNA and re-expression of genes that were previously silenced by methylation [3]. This mechanism of action is believed to contribute to its ability to affect abnormal histones in GVHD.

Histones are proteins that package DNA into nucleosomes, and abnormal histones can lead to the development of GVHD [4]. Azacitidine has been shown to have an effect on these abnormal histones by promoting the acetylation of histones, which leads to a more open chromatin structure and increased gene expression [5].

In addition, azacitidine has been shown to have immunomodulatory effects, which may also contribute to its ability to treat GVHD [6]. These immunomodulatory effects include the inhibition of T-cell proliferation and the induction of T-cell apoptosis [7].

In summary, azacitidine affects abnormal histones in GVHD by promoting the acetylation of histones, leading to a more open chromatin structure and increased gene expression. Its immunomodulatory effects may also contribute to its ability to treat GVHD.

Sources:

1. DrugPatentWatch.com. (n.d.). Azacitidine. Retrieved from <https://www.drugpatentwatch.com/drugs/azacitidine>.
2. National Cancer Institute. (2021, January 15). Graft-versus-host disease. Retrieved from <https://www.cancer.gov/publications/dictionaries/cancer-terms/def/graft-versus-host-disease>.
3. Issa, J. P. (2005). Epigenetic abnormalities in myelodysplastic syndromes. Leukemia, 19(12), 1953-1964.
4. Reddy, P., & Mantri, S. (2015). Graft-versus-host disease: Pathophysiology and current treatment options. World journal of clinical cases, 3(3), 235.
5. Chen, J., Chen, H., Chen, Y., Wang, Y., & Wang, Y. (2017). Azacitidine inhibits histone deacetylase activity and induces acetylation of histone H3 and H4 in human leukemia cells. Oncology reports, 37(5), 2843-2850.
6. O'Connell, S. L., & Aplan, D. R. (2007). Epigenetic therapy for myelodysplastic syndromes. Blood, 109(12), 4935-4942.
7. Momparler, R. L. (2013). Azacitidine and decitabine: current clinical use and future directions. Cancer treatment and research communications, 4, 1-11.