Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning.
Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning.
复制标题
药物发现和药物重新定位中的三维体外细胞培养模型。
DOI：
10.3389/fphar.2018.00006
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发表时间：
2018
影响因子：
5.6
通讯作者：
Langhans SA
中科院分区：
文献类型：
--
作者：
Langhans SA
药物开发是一个漫长而昂贵的过程，经历了几个阶段，从靶标确定到领先的发现和优化，临床前验证和临床试验，最终批准用于临床。这一过程中的一个重要步骤是对小型化合物文库进行高通量筛选(HTS)以进行铅鉴定。目前，大多数基于细胞的高温超导是在组织培养优化的塑料表面上以二维(2D)培养的培养细胞上进行的。与此同时，令人信服的证据表明，在这些非生理性条件下培养的细胞并不代表存在于组织复杂微环境中的细胞。这种差异被认为是导致药物发现失败率高的一个重要原因，在被调查的药物中，只有很低比例的药物能够通过一系列测试和上市审批。因此，更接近体内细胞环境的三维(3D)细胞培养技术现在正受到密切关注，因为它们有望在药物发现中适应更高的精确度。在这里，我们将回顾3D培养的常见方法，讨论3D培养在耐药性和药物重新定位中的意义，并解决将3D细胞培养应用于高通量药物发现的一些挑战。
Drug development is a lengthy and costly process that proceeds through several stages from target identification to lead discovery and optimization, preclinical validation and clinical trials culminating in approval for clinical use. An important step in this process is high-throughput screening (HTS) of small compound libraries for lead identification. Currently, the majority of cell-based HTS is being carried out on cultured cells propagated in two-dimensions (2D) on plastic surfaces optimized for tissue culture. At the same time, compelling evidence suggests that cells cultured in these non-physiological conditions are not representative of cells residing in the complex microenvironment of a tissue. This discrepancy is thought to be a significant contributor to the high failure rate in drug discovery, where only a low percentage of drugs investigated ever make it through the gamut of testing and approval to the market. Thus, three-dimensional (3D) cell culture technologies that more closely resemble in vivo cell environments are now being pursued with intensity as they are expected to accommodate better precision in drug discovery. Here we will review common approaches to 3D culture, discuss the significance of 3D cultures in drug resistance and drug repositioning and address some of the challenges of applying 3D cell cultures to high-throughput drug discovery.
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影响因子：
5.8
作者：
Banks, Jessica M.;Harley, Brendan A. C.;Bailey, Ryan C.
通讯作者：
Bailey, Ryan C.
PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
DOI：
10.14573/altex.1406111
发表时间：
2014
期刊：
ALTEX
影响因子：
--
作者：
Alépée N;Bahinski A;Daneshian M;De Wever B;Fritsche E;Goldberg A;Hansmann J;Hartung T;Haycock J;Hogberg H;Hoelting L;Kelm JM;Kadereit S;McVey E;Landsiedel R;Leist M;Lübberstedt M;Noor F;Pellevoisin C;Petersohn D;Pfannenbecker U;Reisinger K;Ramirez T;Rothen-Rutishauser B;Schäfer-Korting M;Zeilinger K;Zurich MG
通讯作者：
Zurich MG
影响因子：
41.2
作者：
Caiazzo, Massimiliano;Okawa, Yuya;Lutolf, Matthias P.
通讯作者：
Lutolf, Matthias P.
影响因子：
7.2
作者：
Barros, Claudia S.;Franco, Santos J.;Mueller, Ulrich
通讯作者：
Mueller, Ulrich