TY  - JOUR
AU  - Đoković, Nemanja
AU  - Rahnasto-Rilla, Minna
AU  - Lougiakis, Nikolas
AU  - Lahtela-Kakkonen, Maija
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4416
AB  - A growing body of preclinical evidence recognized selective sirtuin 2 (SIRT2) inhibitors as novel therapeutics for treatment of age-related diseases. However, none of the SIRT2 inhibitors have reached clinical trials yet. Transformative potential of machine learning (ML) in early stages of drug discovery has been witnessed by widespread adoption of these techniques in recent years. Despite great potential, there is a lack of robust and large-scale ML models for discovery of novel SIRT2 inhibitors. In order to support virtual screening (VS), lead optimization, or facilitate the selection of SIRT2 inhibitors for experimental evaluation, a machine-learning-based tool titled SIRT2i_Predictor was developed. The tool was built on a panel of high-quality ML regression and classification-based models for prediction of inhibitor potency and SIRT1-3 isoform selectivity. State-of-the-art ML algorithms were used to train the models on a large and diverse dataset containing 1797 compounds. Benchmarking against structure-based VS protocol indicated comparable coverage of chemical space with great gain in speed. The tool was applied to screen the in-house database of compounds, corroborating the utility in the prioritization of compounds for costly in vitro screening campaigns. The easy-to-use web-based interface makes SIRT2i_Predictor a convenient tool for the wider community. The SIRT2i_Predictor’s source code is made available online.
PB  - MDPI
T2  - Pharmaceuticals
T1  - SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors
VL  - 16
IS  - 1
DO  - 10.3390/ph16010127
ER  - 

@article{
author = "Đoković, Nemanja and Rahnasto-Rilla, Minna and Lougiakis, Nikolas and Lahtela-Kakkonen, Maija and Nikolić, Katarina",
year = "2023",
abstract = "A growing body of preclinical evidence recognized selective sirtuin 2 (SIRT2) inhibitors as novel therapeutics for treatment of age-related diseases. However, none of the SIRT2 inhibitors have reached clinical trials yet. Transformative potential of machine learning (ML) in early stages of drug discovery has been witnessed by widespread adoption of these techniques in recent years. Despite great potential, there is a lack of robust and large-scale ML models for discovery of novel SIRT2 inhibitors. In order to support virtual screening (VS), lead optimization, or facilitate the selection of SIRT2 inhibitors for experimental evaluation, a machine-learning-based tool titled SIRT2i_Predictor was developed. The tool was built on a panel of high-quality ML regression and classification-based models for prediction of inhibitor potency and SIRT1-3 isoform selectivity. State-of-the-art ML algorithms were used to train the models on a large and diverse dataset containing 1797 compounds. Benchmarking against structure-based VS protocol indicated comparable coverage of chemical space with great gain in speed. The tool was applied to screen the in-house database of compounds, corroborating the utility in the prioritization of compounds for costly in vitro screening campaigns. The easy-to-use web-based interface makes SIRT2i_Predictor a convenient tool for the wider community. The SIRT2i_Predictor’s source code is made available online.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors",
volume = "16",
number = "1",
doi = "10.3390/ph16010127"
}

Đoković, N., Rahnasto-Rilla, M., Lougiakis, N., Lahtela-Kakkonen, M.,& Nikolić, K.. (2023). SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors. in Pharmaceuticals
MDPI., 16(1).
https://doi.org/10.3390/ph16010127

Đoković N, Rahnasto-Rilla M, Lougiakis N, Lahtela-Kakkonen M, Nikolić K. SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors. in Pharmaceuticals. 2023;16(1).
doi:10.3390/ph16010127 .

Đoković, Nemanja, Rahnasto-Rilla, Minna, Lougiakis, Nikolas, Lahtela-Kakkonen, Maija, Nikolić, Katarina, "SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors" in Pharmaceuticals, 16, no. 1 (2023),
https://doi.org/10.3390/ph16010127 . .