Description
MGCD-0103 is a benzamide histone deacetylase (HDAC) inhibitor that exhibits anticancer chemotherapeutic, anti-fibrotic, antihypertensive, and cardiomodulatory activities. MGCD-0103 is currently in clinical trials as a potential treatment for several leukemias and lymphomas. In sham hearts, MGCD-0103 improves left ventricular and end diastolic pressure and decreases total collagen levels; in CD90+ cells, it decreases levels of collagen III, matrix metalloproteinase 2, and α-SMA. In other models, MGCD-0103 increases natriuretic peptide receptor (NPR1) promoter activity, increasing transcription of guanyl cyclase A/natriuretic peptide receptor A. MGCD-0103 also decreases pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in animal models of myocardial infarction and heart failure. Additionally, this compound induces apoptosis, activates PI3K/Akt/mTOR signaling, and decreases autophagy in chronic lymphocytic leukemia (CLL) cells.
References
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Kumar P, Tripathi S, Pandey KN. Histone deacetylase inhibitors modulate the transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-a gene: interactive roles of modified histones, histone acetyltransferase, p300, AND Sp1. J Biol Chem. 2014 Mar 7;289(10):6991-7002. PMID: 24451378.
El-Khoury V, Pierson S, Szwarcbart E, et al. Disruption of autophagy by the histone deacetylase inhibitor MGCD0103 and its therapeutic implication in B-cell chronic lymphocytic leukemia. Leukemia. 2014 Aug;28(8):1636-46. PMID: 24418989.
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