Search results for " pharmacophore modelling"
showing 3 items of 3 documents
Repurposing old drugs to fight multidrug resistant cancers.
2020
Overcoming multidrug resistance represents a major challenge for cancer treatment. In the search for new chemotherapeutics to treat malignant diseases, drug repurposing gained a tremendous interest during the past years. Repositioning candidates have often emerged through several stages of clinical drug development, and may even be marketed, thus attracting the attention and interest of pharmaceutical companies as well as regulatory agencies. Typically, drug repositioning has been serendipitous, using undesired side effects of small molecule drugs to exploit new disease indications. As bioinformatics gain increasing popularity as an integral component of drug discovery, more rational approa…
TOWARD ENRICHED VHTS FOR CDK2 INHIBITORS: MOLECULAR DYNAMICS, PHARMACOPHORE MODELLING, AND DOCKING
2019
Cyclin-Dependent Kinases-2 (CDK2) are members of the serine/threonine protein kinases family. They play an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidence indicates that excessive expression of CDK2s should cause abnormal cell cycle regulation. Therefore, since a long time, CDK2s have been considered potential therapeutic targets for cancer therapy. In this work, we collected one-hundred and forty-nine complexes of inhibitors bound in the CDK2-ATP pocket submitting to short MD simulations (10ns) and free energy calculation by means of MM-GBSA. The calculate ∆G values have been compared with …
CHA on CDK2: a way to identify the best pharmacophore model for the virtual screening of new inhibitors
2018
Cyclin-dependent kinase-2 (CDK2) is a member of serine/threonine protein kinases family. It plays an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidences indicate that excessive expression of CDK2 should cause abnormal cell cycle regulation. Therefore, CDK2 has been considered a potential therapeutic target for cancer therapy. In this work, we used a modelling approach that incorporates flexibility based on extensive MD simulations of protein−ligand complexes into structure-based pharmacophore modeling and virtual screening to identify new CDK2 inhibitors. One-hundred and forty-nine CDK2-inhibit…