Abstract
Pancreatic cancer (PANC) is a dangerous type of cancer that is a major cause of mortality worldwide and exhibits a remarkably poor prognosis. To date, discovering anti-PANC agents remains a very complex and expensive process. Computational approaches can accelerate the search for anti-PANC agents. We report for the first time two models that combined perturbation theory with machine learning via a multilayer perceptron network (PTML-MLP) to perform the virtual design and prediction of molecules that can simultaneously inhibit multiple PANC cell lines and PANC-related proteins, such as caspase-1, tumor necrosis factor-alpha (TNF-alpha), and the insulin-like growth factor 1 receptor (IGF1R). Both PTML-MLP models exhibited accuracies higher than 78%. Using the interpretation from one of the PTML-MLP models as a guideline, we extracted different molecular fragments desirable for the inhibition of the PANC cell lines and the aforementioned PANC-related proteins and then assembled some of those fragments to form three new molecules. The two PTML-MLP models predicted the designed molecules as potentially versatile anti-PANC agents through inhibition of the three PANC-related proteins and multiple PANC cell lines. Conclusions: This work opens new horizons for the application of the PTML modeling methodology to anticancer research.