Combination of Gemcitabine with Cell-Penetrating Peptides: A Pharmacokinetic Approach Using In Silico Tools
Gemcitabine is an anticancer drug used to treat a wide range of solid tumors and is a first line treatment for pancreatic cancer. Our group has previously developed novel conjugates of gemcitabine with cell-penetrating peptides (CPP), and here we report some preliminary data regarding the pharmacoki...
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| Published in: | Biomolecules (Basel, Switzerland) Vol. 9; no. 11; p. 693 |
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| Language: | English |
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| Abstract | Gemcitabine is an anticancer drug used to treat a wide range of solid tumors and is a first line treatment for pancreatic cancer. Our group has previously developed novel conjugates of gemcitabine with cell-penetrating peptides (CPP), and here we report some preliminary data regarding the pharmacokinetics of gemcitabine, two gemcitabine-CPP conjugates and respective CPP gathered from GastroPlus™, and analyze these results considering our previous evaluation of gemcitabine release and conjugates' bioactivity. Additionally, seeking to shed some light on the relation between the penetration ability of CPP and their physicochemical properties, chemical descriptors for the 20 natural amino acids were calculated, a new principal property scale (z-scale) was created and CPP prediction models were developed, establishing quantitative structure-activity relationships (QSAR). The z-scores of the peptides conjugated with gemcitabine are presented and analyzed with the aforementioned data. |
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| AbstractList | Gemcitabine is an anticancer drug used to treat a wide range of solid tumors and is a first line treatment for pancreatic cancer. Our group has previously developed novel conjugates of gemcitabine with cell-penetrating peptides (CPP), and here we report some preliminary data regarding the pharmacokinetics of gemcitabine, two gemcitabine-CPP conjugates and respective CPP gathered from GastroPlus™, and analyze these results considering our previous evaluation of gemcitabine release and conjugates’ bioactivity. Additionally, seeking to shed some light on the relation between the penetration ability of CPP and their physicochemical properties, chemical descriptors for the 20 natural amino acids were calculated, a new principal property scale (z-scale) was created and CPP prediction models were developed, establishing quantitative structure-activity relationships (QSAR). The z-scores of the peptides conjugated with gemcitabine are presented and analyzed with the aforementioned data. |
| Author | Ferreira, Abigail Lapa, Rui Vale, Nuno |
| AuthorAffiliation | 3 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal 2 LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; ruilapa@ff.up.pt 4 Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal 1 Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; nuno.vale@ff.up.pt 5 Department of Molecular Pathology and Immunology, Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal |
| AuthorAffiliation_xml | – name: 2 LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; ruilapa@ff.up.pt – name: 1 Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; nuno.vale@ff.up.pt – name: 3 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal – name: 4 Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal – name: 5 Department of Molecular Pathology and Immunology, Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal |
| Author_xml | – sequence: 1 givenname: Abigail surname: Ferreira fullname: Ferreira, Abigail email: abigail.ferreira@fc.up.pt, abigail.ferreira@fc.up.pt organization: LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. abigail.ferreira@fc.up.pt – sequence: 2 givenname: Rui surname: Lapa fullname: Lapa, Rui email: ruilapa@ff.up.pt organization: LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. ruilapa@ff.up.pt – sequence: 3 givenname: Nuno surname: Vale fullname: Vale, Nuno email: nuno.vale@ff.up.pt, nuno.vale@ff.up.pt, nuno.vale@ff.up.pt, nuno.vale@ff.up.pt organization: Department of Molecular Pathology and Immunology, Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. nuno.vale@ff.up.pt |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31690028$$D View this record in MEDLINE/PubMed |
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| Keywords | pharmacokinetics cell-penetrating peptides (CPP) z-scale gemcitabine GastroPlus in silico |
| Language | English |
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| Title | Combination of Gemcitabine with Cell-Penetrating Peptides: A Pharmacokinetic Approach Using In Silico Tools |
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