<br>COTI-2 是一种新型小分子，在体外和体内对多种人类癌细胞系具有活性。,Oncotarget

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COTI-2 是一种新型小分子，在体外和体内对多种人类癌细胞系具有活性。
Oncotarget Pub Date : 2016-07-05 , DOI: 10.18632/oncotarget.9133
Kowthar Y Salim ₁ , Saman Maleki Vareki ₂ , Wayne R Danter ₁ , James Koropatnick _{2,

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Affiliation

鉴定高效低毒的新型抗癌化合物对于药物开发至关重要。高通量筛选和其他此类策略通常是资源密集型的。因此，计算机辅助药物设计已迅速得到接受和普及。我们采用了专有的计算平台 (CHEMSAS®)，该平台采用传统和现代药理学原理、统计模型、药物化学和机器学习技术的独特组合来发现和优化可针对各种癌症的新型化合物。 COTI-2 是使用 CHEMSAS 鉴定的一种小分子候选抗癌药物。本研究描述了 COTI-2 的体外和体内评估。我们的数据表明，COTI-2 可有效对抗多种人类癌细胞系，无论其组织来源或基因组成如何。大多数经处理的癌细胞系对纳摩尔浓度的 COTI-2 敏感。与传统化疗或靶向治疗药物相比，COTI-2 在体外和体内均表现出优异的抗肿瘤细胞活性。尽管 COTI-2 具有强大的抗肿瘤功效，但其在体内是安全且耐受性良好的。虽然COTI-2的作用机制仍在研究中，但初步结果表明它不是传统的激酶或Hsp90抑制剂。

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COTI-2, a novel small molecule that is active against multiple human cancer cell lines in vitro and in vivo.

Identification of novel anti-cancer compounds with high efficacy and low toxicity is critical in drug development. High-throughput screening and other such strategies are generally resource-intensive. Therefore, in silico computer-aided drug design has gained rapid acceptance and popularity. We employed our proprietary computational platform (CHEMSAS®), which uses a unique combination of traditional and modern pharmacology principles, statistical modeling, medicinal chemistry, and machine-learning technologies to discover and optimize novel compounds that could target various cancers. COTI-2 is a small molecule candidate anti-cancer drug identified using CHEMSAS. This study describes the in vitro and in vivo evaluation of COTI-2. Our data demonstrate that COTI-2 is effective against a diverse group of human cancer cell lines regardless of their tissue of origin or genetic makeup. Most treated cancer cell lines were sensitive to COTI-2 at nanomolar concentrations. When compared to traditional chemotherapy or targeted-therapy agents, COTI-2 showed superior activity against tumor cells, in vitro and in vivo. Despite its potent anti-tumor efficacy, COTI-2 was safe and well-tolerated in vivo. Although the mechanism of action of COTI-2 is still under investigation, preliminary results indicate that it is not a traditional kinase or an Hsp90 inhibitor.

更新日期：2019-11-01

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