Metabolic stability and its role in the discovery of new chemical entities
Determination of metabolic profiles of new chemical entities is a key step in the process of drug discovery, since it influences pharmacokinetic characteristics of therapeutic compounds. One of the main challenges of medicinal chemistry is not only to design compounds demonstrating beneficial activi...
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| Format: | Article |
| Language: | English |
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Sciendo
2019-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2019-0024 |
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| author | Słoczyńska Karolina Gunia-Krzyżak Agnieszka Koczurkiewicz Paulina Wójcik-Pszczoła Katarzyna Żelaszczyk Dorota Popiół Justyna Pękala Elżbieta |
| author_facet | Słoczyńska Karolina Gunia-Krzyżak Agnieszka Koczurkiewicz Paulina Wójcik-Pszczoła Katarzyna Żelaszczyk Dorota Popiół Justyna Pękala Elżbieta |
| author_sort | Słoczyńska Karolina |
| collection | DOAJ |
| description | Determination of metabolic profiles of new chemical entities is a key step in the process of drug discovery, since it influences pharmacokinetic characteristics of therapeutic compounds. One of the main challenges of medicinal chemistry is not only to design compounds demonstrating beneficial activity, but also molecules exhibiting favourable pharmacokinetic parameters. Chemical compounds can be divided into those which are metabolized relatively fast and those which undergo slow biotransformation. Rapid biotransformation reduces exposure to the maternal compound and may lead to the generation of active, non-active or toxic metabolites. In contrast, high metabolic stability may promote interactions between drugs and lead to parent compound toxicity. In the present paper, issues of compound metabolic stability will be discussed, with special emphasis on its significance, in vitro metabolic stability testing, dilemmas regarding in vitro-in vivo extrapolation of the results and some aspects relating to different preclinical species used in in vitro metabolic stability assessment of compounds. |
| format | Article |
| id | doaj-art-e57750af5bbc4d719f94fa00aa24f232 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2019-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-e57750af5bbc4d719f94fa00aa24f2322025-02-02T00:31:54ZengSciendoActa Pharmaceutica1846-95582019-09-0169334536110.2478/acph-2019-0024acph-2019-0024Metabolic stability and its role in the discovery of new chemical entitiesSłoczyńska Karolina0Gunia-Krzyżak Agnieszka1Koczurkiewicz Paulina2Wójcik-Pszczoła Katarzyna3Żelaszczyk Dorota4Popiół Justyna5Pękala Elżbieta6Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688Krakow, PolandDepartment of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688Krakow, PolandDepartment of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688Krakow, PolandDepartment of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688Krakow, PolandDepartment of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688Krakow, PolandDepartment of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688Krakow, PolandDepartment of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688Krakow, PolandDetermination of metabolic profiles of new chemical entities is a key step in the process of drug discovery, since it influences pharmacokinetic characteristics of therapeutic compounds. One of the main challenges of medicinal chemistry is not only to design compounds demonstrating beneficial activity, but also molecules exhibiting favourable pharmacokinetic parameters. Chemical compounds can be divided into those which are metabolized relatively fast and those which undergo slow biotransformation. Rapid biotransformation reduces exposure to the maternal compound and may lead to the generation of active, non-active or toxic metabolites. In contrast, high metabolic stability may promote interactions between drugs and lead to parent compound toxicity. In the present paper, issues of compound metabolic stability will be discussed, with special emphasis on its significance, in vitro metabolic stability testing, dilemmas regarding in vitro-in vivo extrapolation of the results and some aspects relating to different preclinical species used in in vitro metabolic stability assessment of compounds.https://doi.org/10.2478/acph-2019-0024metabolic stabilitybiotransformationintrinsic clearancein vitro half-lifemetabolitesnew chemical entity |
| spellingShingle | Słoczyńska Karolina Gunia-Krzyżak Agnieszka Koczurkiewicz Paulina Wójcik-Pszczoła Katarzyna Żelaszczyk Dorota Popiół Justyna Pękala Elżbieta Metabolic stability and its role in the discovery of new chemical entities Acta Pharmaceutica metabolic stability biotransformation intrinsic clearance in vitro half-life metabolites new chemical entity |
| title | Metabolic stability and its role in the discovery of new chemical entities |
| title_full | Metabolic stability and its role in the discovery of new chemical entities |
| title_fullStr | Metabolic stability and its role in the discovery of new chemical entities |
| title_full_unstemmed | Metabolic stability and its role in the discovery of new chemical entities |
| title_short | Metabolic stability and its role in the discovery of new chemical entities |
| title_sort | metabolic stability and its role in the discovery of new chemical entities |
| topic | metabolic stability biotransformation intrinsic clearance in vitro half-life metabolites new chemical entity |
| url | https://doi.org/10.2478/acph-2019-0024 |
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