Designing of promiscuous inhibitors against pancreatic cancer cell lines
Designing of promiscuous inhibitors against pancreatic cancer cell lines
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DOI：
10.1038/srep04668
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发表时间：
2014-04-14
影响因子：
4.6
通讯作者：
Raghava, Gajendra P. S.
中科院分区：
文献类型：
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作者：
Kumar, Rahul;Chaudhary, Kumardeep;Raghava, Gajendra P. S.
胰腺癌仍然是最具破坏性和预后最差的疾病。目前迫切需要加快药物发现进程，以确定针对胰腺癌的新的有效候选药物。我们利用药理学数据开发了预测混杂抑制剂的QSAR模型。在10倍交叉验证的情况下，我们的模型获得了最大的皮尔逊相关系数0.86。我们的模型还成功地验证了药物与癌基因的关系，并进一步使用这些模型筛选FDA批准的药物并在体外进行测试。我们已经将这些模型集成到一个名为DiPCell的网络服务器中，该服务器将有助于筛选和设计新型混杂药物分子。我们还确定了对胰腺癌细胞株最有效和最不有效的药物。另一方面，我们已经发现了耐药的胰腺癌细胞株，需要对它们进行探索性扫描，以揭示胰腺癌的耐药机制。
Pancreatic cancer remains the most devastating disease with worst prognosis. There is a pressing need to accelerate the drug discovery process to identify new effective drug candidates against pancreatic cancer. We have developed QSAR models for predicting promiscuous inhibitors using the pharmacological data. Our models achieved maximum Pearson correlation coefficient of 0.86, when evaluated on 10-fold cross-validation. Our models have also successfully validated the drug-to-oncogene relationship and further we used these models to screen FDA approved drugs and tested them in vitro. We have integrated these models in a webserver named as DiPCell, which will be useful for screening and designing novel promiscuous drug molecules. We have also identified the most and least effective drugs for pancreatic cancer cell lines. On the other side, we have identified resistant pancreatic cancer cell lines, which need investigative scanner on them to put light on resistant mechanism in pancreatic cancer.