ao8b03693_si_005.xlsx (39.76 kB)
Multicellular Target QSAR Model for Simultaneous Prediction and Design of Anti-Pancreatic Cancer Agents
dataset
posted on 2019-02-12, 14:35 authored by Alejandro Speck-PlanchePancreatic cancers are widely recognized
as a group of neoplasms
with one of the poorest prognoses in oncology research. Despite the
advances achieved in drug design and development, there is no effective
cure for pancreatic cancers, and the current chemotherapeutic regimens
increase the survival rate by only a few months. As an integral part
of all modern drug discovery campaigns, computer-aided approaches
can represent a promising alternative change to accelerate the early
discovery of potent anti-pancreatic cancer agents. To date, however,
most of the efforts made so far have focused on small series of structurally
related chemicals, where the anti-pancreatic cancer activity has been
measured against only one cancer cell line. In addition, no rational
insight has been provided in the sense of unveiling the physicochemical
aspects and the structural features that the molecules should possess
to increase the anti-pancreatic cancer activity. This work reports
the first multicellular target QSAR model based on ensemble learning
(mct-QSAR-EL) that allows the simultaneous prediction and design of
molecules with activity against different pancreatic cancer cell lines,
which exhibit different degrees of sensitivity to chemical treatment.
The mct-QSAR-EL model displayed sensitivities and specificities higher
than 80% in both training and test sets. The physicochemical and structural
interpretations of the molecular descriptors in the model permitted
the selection of several fragments with potentially positive contributions
to the increase of the anti-pancreatic cancer activity. These fragments
were then assembled to design new molecules. The designed molecules
were predicted as multicell line inhibitors by the mct-QSAR-EL model,
and these results converged with the predictions performed by recently
reported models. The designed molecules complied with Lipinski’s
rule of five and its variants.
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pancreatic cancer cell linesMulticellular Target QSAR Modelmct-QSAR-EL modelanti-pancreatic cancer agentscancer cell linemulticellular target QSAR modelAnti-Pancreatic Cancer Agents Pancreatic cancersmoleculedrug discovery campaignsmulticell line inhibitorsanti-pancreatic cancer activitychemotherapeutic regimens increase