Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor.
Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor.
复制标题
DOI：
10.1517/13543784.2011.577737
复制
发表时间：
2011-06
影响因子：
6.1
通讯作者：
Garcia-Manero G
中科院分区：
文献类型：
--
作者：
Boumber Y;Younes A;Garcia-Manero G
HDAC抑制剂（HDACIs）具有恢复基因表达和体外显示抗肿瘤作用的潜力。HDACIs作为单药在淋巴瘤中具有临床活性。在骨髓性白血病中，DNA甲基化抑制剂和HDACIs的组合是有希望的。其他组合正在实体瘤中进行研究。本文涵盖了口服同种型选择性HDACI MGCD 0103（mocetinostat）治疗血液恶性肿瘤和实体瘤的基本信息以及临床前和临床经验的更新。它还检查了最近的会议和文章中关于MGCD 0103的数据，直到2010年11月，包括淋巴瘤和毒性反应的新数据。MGCD 0103耐受性良好，表现出良好的药代动力学和药效学特征，证明了靶点抑制和临床应答。它诱导细胞死亡和自噬，与蛋白酶体抑制剂协同作用，并影响非组蛋白靶点，如微管。2008年，由于潜在的心脏并发症，试验中的新患者招募被暂时停止。由于未发现MGCD 0103暴露与心包积液之间的相关性，该限制于2009年取消。MGCD 0103临床试验的新患者入组要求排除入组前诊断为显著心脏异常的患者。临床和药效学数据支持以90 mg固定剂量每周三次给药。MGCD 0103在几种血液病中显示出有希望的抗肿瘤活性。
HDAC inhibitors (HDACIs) have the potential to restore gene expression and display antitumor effects in vitro. As single agents, HDACIs have clinical activity in lymphoma. In myeloid leukemias, combinations of DNA methylation inhibitors and HDACIs are promising. Other combinations are being studied in solid tumors. This article covers basic information and an update on preclinical and clinical experience with the oral isotype-selective HDACI MGCD0103 (mocetinostat) in hematological malignancies and solid tumors. It also examines data concerning MGCD0103 from recent conferences and articles through to November 2010, including new data regarding responses in lymphoma and toxicities. MGCD0103 is well-tolerated and exhibits favorable pharmacokinetic and pharmacodynamic profiles, demonstrating target inhibition and clinical responses. It induces cell death and autophagy, synergizes with proteasomal inhibitors and affects non-histone targets, such as microtubules. In 2008, new patient enrollment in trials was temporarily suspended due to potential cardiac complications. This restriction was lifted in 2009 as no correlation between MGCD0103 exposure and pericardial effusions was found. New patient enrollment in MGCD0103 clinical trials requires the exclusion of patients diagnosed with significant cardiac abnormalities prior to enrollment. Clinical and pharmacodynamic data support a three-times-weekly administration at a 90 mg fixed dose. MGCD0103 displays promising antitumor activity in several hematological diseases.
登录
查看更多内容
影响因子：
3.3
作者：
Grant C;Rahman F;Piekarz R;Peer C;Frye R;Robey RW;Gardner ER;Figg WD;Bates SE
通讯作者：
Bates SE
影响因子：
11.5
作者：
Fantin, Valeria R.;Richon, Victoria M.
通讯作者：
Richon, Victoria M.
影响因子：
6.5
作者：
Buglio, Daniela;Mamidipudi, Vidya;Younes, Anas
通讯作者：
Younes, Anas
影响因子：
20.3
作者：
Buglio, Daniela;Georgakis, Georgios V.;Younes, Anas
通讯作者：
Younes, Anas
影响因子：
11.5
作者：
Bonfils, Claire;Kalita, Ann;Li, Zuomei
通讯作者：
Li, Zuomei