The polar surface area (PSA) or topological polar surface area (TPSA) of a molecule is defined as the surface sum over all polar atoms or molecules, primarily oxygen and nitrogen, also including their attached hydrogen atoms.
Electrical potential surface of paracetamol showing polar areas in red and blue
PSA is a commonly used medicinal chemistry metric for the optimization of a drug's ability to permeate cells. Molecules with a polar surface area of greater than 140 angstroms squared (Å2) tend to be poor at permeating cell membranes.[1] For molecules to penetrate the blood–brain barrier (and thus act on receptors in the central nervous system), a PSA less than 90 Å2 is usually needed.[2]
TPSA is a valuable tool in drug discovery and development. By analyzing a drug candidate's TPSA, scientists can predict its potential for oral bioavailability and ability to reach target sites within the body. This prediction hinges on a drug's ability to permeate biological barriers.
Permeating these barriers, such as the Blood-Brain Barrier (BBB), the Placental Barrier (PB), and the Blood-Mammary Barrier (BM), is crucial for many drugs to reach their intended targets.
The BBB, for example, protects the brain from harmful substances. Drugs with a lower TPSA (generally below 90 Ų) tend to permeate the BBB more easily, allowing them to reach the brain and exert their therapeutic effects (Shityakov et al[3]., 2013).
Similarly, for drugs intended to treat the fetus, a lower TPSA (below 60 Ų) is preferred to ensure they can pass through the placenta (Augustiño-Roubina[4] et al., 2019).
Breastfeeding mothers also need consideration. Here, an optimal TPSA for a drug is around 60-80 Ų to allow it to reach the breast tissue for milk production, while drugs exceeding 90 Ų are less likely to permeate the Blood-Mammary Barrier.[5]
^Pajouhesh H, Lenz GR (Oct 2005). "Medicinal Chemical Properties of Successful Central Nervous System Drugs". NeuroRx. 2 (4): 541–553. doi:10.1602/neurorx.2.4.541. PMC1201314. PMID 16489364.
^Hitchcock SA, Pennington LD (May 2006). "Structure - Brain Exposure Relationships". J. Med. Chem. 49 (26): 7559–7583. doi:10.1021/jm060642i. PMID 17181137.
^Shityakov, Sergey; Neuhaus, Winfried; Dandekar, Thomas; Förster, Carola (2013). "Analysing molecular polar surface descriptors to predict blood-brain barrier permeation". International Journal of Computational Biology and Drug Design. 6 (1–2): 146–156. doi:10.1504/IJCBDD.2013.052195. ISSN 1756-0756. PMID 23428480.
^Hester, Gabrielle; Lang, Tom; Madsen, Laura; Tambyraja, Rabindra; Zenker, Paul (January 2019). "Timely Data for Targeted Quality Improvement Interventions: Use of a Visual Analytics Dashboard for Bronchiolitis". Applied Clinical Informatics. 10 (1): 168–174. doi:10.1055/s-0039-1679868. ISSN 1869-0327. PMC6402943. PMID 30841007.
Pajouhesh, Hassan; Lenz, George R (2005). "Medicinal chemical properties of successful central nervous system drugs". NeuroRx. 2 (4): 541–553. doi:10.1602/neurorx.2.4.541. PMC1201314. PMID 16489364.
Clark, David E (1999). "Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption". Journal of Pharmaceutical Sciences. 88 (8): 807–14. doi:10.1021/js9804011. PMID 10430547.
Palm, Katrin; Stenberg, Patric; Luthman, Kristina; Artursson1, Per (1997). "Polar molecular surface properties predict the intestinal absorption of drugs in humans". Pharmaceutical Research. 14 (5): 568–71. doi:10.1023/A:1012188625088. PMID 9165525. S2CID 7178582.{{cite journal}}: CS1 maint: numeric names: authors list (link)
Ertl, Peter; Rohde, Bernhard; Selzer, Paul (2000). "Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties". Journal of Medicinal Chemistry. 43 (20): 3714–3717. doi:10.1021/jm000942e. PMID 11020286.
Ertl, P. Polar Surface Area, in Molecular Drug Properties, R. Mannhold (ed), Wiley-VCH, pp. 111–126, 2007
Shityakov, Sergey; Neuhaus, Winfried; Dandekar, Thomas; Förster, Carola (2013). "Analysing molecular polar surface descriptors to predict blood-brain barrier permeation". International Journal of Computational Biology and Drug Design. 6 (1–2): 146–56. doi:10.1504/IJCBDD.2013.052195. PMID 23428480.
External linksedit
Interactive Polar Surface Area calculator
Free, Programmable TPSA Calculator
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This article includes a list of general references but it lacks sufficient corresponding inline citations Please help to improve this article by introducing more precise citations December 2017 Learn how and when to remove this message The polar surface area PSA or topological polar surface area TPSA of a molecule is defined as the surface sum over all polar atoms or molecules primarily oxygen and nitrogen also including their attached hydrogen atoms Electrical potential surface of paracetamol showing polar areas in red and blue PSA is a commonly used medicinal chemistry metric for the optimization of a drug s ability to permeate cells Molecules with a polar surface area of greater than 140 angstroms squared A2 tend to be poor at permeating cell membranes 1 For molecules to penetrate the blood brain barrier and thus act on receptors in the central nervous system a PSA less than 90 A2 is usually needed 2 TPSA is a valuable tool in drug discovery and development By analyzing a drug candidate s TPSA scientists can predict its potential for oral bioavailability and ability to reach target sites within the body This prediction hinges on a drug s ability to permeate biological barriers Permeating these barriers such as the Blood Brain Barrier BBB the Placental Barrier PB and the Blood Mammary Barrier BM is crucial for many drugs to reach their intended targets The BBB for example protects the brain from harmful substances Drugs with a lower TPSA generally below 90 A tend to permeate the BBB more easily allowing them to reach the brain and exert their therapeutic effects Shityakov et al 3 2013 Similarly for drugs intended to treat the fetus a lower TPSA below 60 A is preferred to ensure they can pass through the placenta Augustino Roubina 4 et al 2019 Breastfeeding mothers also need consideration Here an optimal TPSA for a drug is around 60 80 A to allow it to reach the breast tissue for milk production while drugs exceeding 90 A are less likely to permeate the Blood Mammary Barrier 5 Contents 1 See also 2 References 3 Literature 4 External linksSee also editBiopharmaceutics Classification System Cheminformatics Chemistry Development Kit JOELib Implicit solvation Lipinski s rule of fiveReferences edit Pajouhesh H Lenz GR Oct 2005 Medicinal Chemical Properties of Successful Central Nervous System Drugs NeuroRx 2 4 541 553 doi 10 1602 neurorx 2 4 541 PMC 1201314 PMID 16489364 Hitchcock SA Pennington LD May 2006 Structure Brain Exposure Relationships J Med Chem 49 26 7559 7583 doi 10 1021 jm060642i PMID 17181137 Shityakov Sergey Neuhaus Winfried Dandekar Thomas Forster Carola 2013 Analysing molecular polar surface descriptors to predict blood brain barrier permeation International Journal of Computational Biology and Drug Design 6 1 2 146 156 doi 10 1504 IJCBDD 2013 052195 ISSN 1756 0756 PMID 23428480 Hester Gabrielle Lang Tom Madsen Laura Tambyraja Rabindra Zenker Paul January 2019 Timely Data for Targeted Quality Improvement Interventions Use of a Visual Analytics Dashboard for Bronchiolitis Applied Clinical Informatics 10 1 168 174 doi 10 1055 s 0039 1679868 ISSN 1869 0327 PMC 6402943 PMID 30841007 Drastikh PARACETAMOL farmako net Retrieved 2024 04 10 Literature editPajouhesh Hassan Lenz George R 2005 Medicinal chemical properties of successful central nervous system drugs NeuroRx 2 4 541 553 doi 10 1602 neurorx 2 4 541 PMC 1201314 PMID 16489364 Clark David E 1999 Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena 1 Prediction of intestinal absorption Journal of Pharmaceutical Sciences 88 8 807 14 doi 10 1021 js9804011 PMID 10430547 Palm Katrin Stenberg Patric Luthman Kristina Artursson1 Per 1997 Polar molecular surface properties predict the intestinal absorption of drugs in humans Pharmaceutical Research 14 5 568 71 doi 10 1023 A 1012188625088 PMID 9165525 S2CID 7178582 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint numeric names authors list link Ertl Peter Rohde Bernhard Selzer Paul 2000 Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment Based Contributions and Its Application to the Prediction of Drug Transport Properties Journal of Medicinal Chemistry 43 20 3714 3717 doi 10 1021 jm000942e PMID 11020286 Ertl P Polar Surface Area in Molecular Drug Properties R Mannhold ed Wiley VCH pp 111 126 2007 Shityakov Sergey Neuhaus Winfried Dandekar Thomas Forster Carola 2013 Analysing molecular polar surface descriptors to predict blood brain barrier permeation International Journal of Computational Biology and Drug Design 6 1 2 146 56 doi 10 1504 IJCBDD 2013 052195 PMID 23428480 External links editInteractive Polar Surface Area calculator Free Programmable TPSA Calculator nbsp This chemistry related article is a stub You can help Wikipedia by expanding it vte nbsp This computer science article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index 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