High Mobility Group Box-1 (HMGb1): Current Wisdom and Advancement as a Potential Drug Target,Journal of Medicinal Chemistry

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High Mobility Group Box-1 (HMGb1): Current Wisdom and Advancement as a Potential Drug Target
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-12-21 00:00:00 , DOI: 10.1021/acs.jmedchem.7b01136
Sonya VanPatten ₁ , Yousef Al-Abed ₁

Affiliation

High mobility group box-1 (HMGb1) protein, a nuclear non-histone protein that is released or secreted from the cell in response to damage or stress, is a sentinel for the immune system that plays a critical role in cell survival/death pathways. This review highlights key features of the endogenous danger-associated molecular pattern (DAMP) protein, HMGb1 in the innate inflammatory response along with various cofactors and receptors that regulate its downstream effects. The evidence demonstrating increased levels of HMGb1 in human inflammatory diseases and conditions is presented, along with a summary of current small molecule or peptide-like antagonists proven to specifically target HMGb1. Additionally, we delineate the measures needed toward validating this protein as a clinically relevant biomarker or bioindicator and as a relevant drug target.

中文翻译：

高迁移率族Box-1（HMGb1）：当前的智慧和进步作为潜在的药物靶标

高迁移率族box-1（HMGb1）蛋白是一种核非组蛋白，可响应损伤或压力从细胞中释放或分泌，是免疫系统的前哨，在细胞存活/死亡途径中起着至关重要的作用。这篇综述强调了先天性炎症反应中的内源性危险相关分子模式（DAMP）蛋白HMGb1以及调节其下游作用的各种辅因子和受体的关键特征。提供了证明人类炎症性疾病和病症中HMGb1水平升高的证据，以及目前被证明可特异性靶向HMGb1的小分子或肽样拮抗剂的概述。此外，我们描述了验证该蛋白作为临床相关生物标志物或生物指示剂以及相关药物靶标所需的措施。

更新日期：2017-12-21

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