Macrophage Heterogeneity in NASH: More Than Just Nomenclature.
Macrophage Heterogeneity in NASH: More Than Just Nomenclature.
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DOI：
10.1002/hep.31790
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Malhi H
中科院分区：
文献类型：
--
作者：
Parthasarathy G;Malhi H
515 ubrogepant（Ubrelvy）最近获得许可，具有可接受的临床安全性。此外，体外BA-LRA能够区分肝脏安全性和肝毒性结构类似物（例如，氯氮平和奥氮平），（3）表明这种更高通量的方法可用作第二阶段筛选，用于探测化合物的化学空间并确定疗效和毒性的结构基础是否可以分离，特别是在标准一线CRM筛选中标记的化合物的情况下。总的来说，默克公司开创的方法很可能被一些公司在特定环境中视为有价值的，这本身就被视为一个行业的重大成就，迄今为止，该行业在很大程度上不愿意在药物安全筛选中采用基因表达技术。(7)BA-LRA与其他专利化合物组和特定案例研究的性能验证将是实现这一目标的重要一步。尽管如此，这些和其他进展可能会提供更多的机制信息和改善对人类DILI风险的预测，从而降低临床试验中意外DILI的发生率，并提高选择肝脏安全化合物作为新药进一步开发的能力。
515 ubrogepant (Ubrelvy), was recently licensed with an acceptable clinical safety profile. In addition, the in vitro BA-LRA was able to distinguish liver-safe and hepatotoxic structural analogues (eg, clozapine and olanzapine),(3) suggesting that this higher throughput approach could be used as a second stage screen for probing a compound’s chemical space and determining whether the structural bases of efficacy and toxicity can be dissociated, particularly in the case of compounds flagged in standard, frontline CRM screens. Taken together, the approach pioneered by Merck is likely to be seen as valuable by some companies in selected settings, which in itself would be regarded as a major achievement in an industry that has, to date, been largely reluctant to embrace gene expression technology within drug safety screening.(7) Validation of the performance of the BA-LRA with other proprietary compound sets and specific case studies will be an important step toward this goal. Nevertheless, there is potential that these and other advances will provide greater mechanistic information and improved prediction of human DILI risk, thereby lowering the incidence of unexpected DILI in clinical trials and improving the ability to select liver-safe compounds for further development as new medicines.
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DOI：
10.1002/hep.29477
发表时间：
2018-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Friedman SL;Ratziu V;Harrison SA;Abdelmalek MF;Aithal GP;Caballeria J;Francque S;Farrell G;Kowdley KV;Craxi A;Simon K;Fischer L;Melchor-Khan L;Vest J;Wiens BL;Vig P;Seyedkazemi S;Goodman Z;Wong VW;Loomba R;Tacke F;Sanyal A;Lefebvre E
通讯作者：
Lefebvre E
影响因子：
32.4
作者：
Tran, Sophie;Baba, Ines;Gautier, Emmanuel L.
通讯作者：
Gautier, Emmanuel L.
影响因子：
25.7
作者：
Tacke, Frank;Zimmermann, Henning W.
通讯作者：
Zimmermann, Henning W.
影响因子：
64.5
作者：
Jaitin, Diego Adhemar;Adlung, Lorenz;Amit, Ido
通讯作者：
Amit, Ido
影响因子：
32.4
作者：
Remmerie A;Martens L;Thoné T;Castoldi A;Seurinck R;Pavie B;Roels J;Vanneste B;De Prijck S;Vanhockerhout M;Binte Abdul Latib M;Devisscher L;Hoorens A;Bonnardel J;Vandamme N;Kremer A;Borghgraef P;Van Vlierberghe H;Lippens S;Pearce E;Saeys Y;Scott CL
通讯作者：
Scott CL