New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs
Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Fernández, D. [verfasserIn] |
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| Format: |
Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017 |
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| Schlagwörter: |
Second-generation bisphosphonates |
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| Anmerkung: |
© Springer International Publishing AG 2017 |
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| Übergeordnetes Werk: |
Enthalten in: Journal of computer aided molecular design - Springer International Publishing, 1987, 31(2017), 7 vom: 19. Juni, Seite 675-688 |
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| Übergeordnetes Werk: |
volume:31 ; year:2017 ; number:7 ; day:19 ; month:06 ; pages:675-688 |
| Links: |
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| DOI / URN: |
10.1007/s10822-017-0034-5 |
|---|
| Katalog-ID: |
OLC2034743512 |
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| 520 | |a Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. | ||
| 650 | 4 | |a Inhibitors | |
| 650 | 4 | |a Second-generation bisphosphonates | |
| 650 | 4 | |a Human farnesyl pyrophosphate synthase | |
| 650 | 4 | |a Molecular dynamics | |
| 650 | 4 | |a Binding free energy | |
| 700 | 1 | |a Ramis, R. |4 aut | |
| 700 | 1 | |a Ortega-Castro, J. |4 aut | |
| 700 | 1 | |a Casasnovas, R. |4 aut | |
| 700 | 1 | |a Vilanova, B. |4 aut | |
| 700 | 1 | |a Frau, J. |4 aut | |
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10.1007/s10822-017-0034-5 doi (DE-627)OLC2034743512 (DE-He213)s10822-017-0034-5-p DE-627 ger DE-627 rakwb eng 570 VZ 12 15,3 ssgn PHARM DE-84 fid BIODIV DE-30 fid Fernández, D. verfasserin aut New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier © Springer International Publishing AG 2017 Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. Inhibitors Second-generation bisphosphonates Human farnesyl pyrophosphate synthase Molecular dynamics Binding free energy Ramis, R. aut Ortega-Castro, J. aut Casasnovas, R. aut Vilanova, B. aut Frau, J. aut Enthalten in Journal of computer aided molecular design Springer International Publishing, 1987 31(2017), 7 vom: 19. Juni, Seite 675-688 (DE-627)130644110 (DE-600)808166-9 (DE-576)018278221 0920-654X nnns volume:31 year:2017 number:7 day:19 month:06 pages:675-688 https://doi.org/10.1007/s10822-017-0034-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-PHARM FID-BIODIV SSG-OLC-MAT SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_70 GBV_ILN_2219 GBV_ILN_4012 AR 31 2017 7 19 06 675-688 |
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10.1007/s10822-017-0034-5 doi (DE-627)OLC2034743512 (DE-He213)s10822-017-0034-5-p DE-627 ger DE-627 rakwb eng 570 VZ 12 15,3 ssgn PHARM DE-84 fid BIODIV DE-30 fid Fernández, D. verfasserin aut New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier © Springer International Publishing AG 2017 Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. Inhibitors Second-generation bisphosphonates Human farnesyl pyrophosphate synthase Molecular dynamics Binding free energy Ramis, R. aut Ortega-Castro, J. aut Casasnovas, R. aut Vilanova, B. aut Frau, J. aut Enthalten in Journal of computer aided molecular design Springer International Publishing, 1987 31(2017), 7 vom: 19. Juni, Seite 675-688 (DE-627)130644110 (DE-600)808166-9 (DE-576)018278221 0920-654X nnns volume:31 year:2017 number:7 day:19 month:06 pages:675-688 https://doi.org/10.1007/s10822-017-0034-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-PHARM FID-BIODIV SSG-OLC-MAT SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_70 GBV_ILN_2219 GBV_ILN_4012 AR 31 2017 7 19 06 675-688 |
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10.1007/s10822-017-0034-5 doi (DE-627)OLC2034743512 (DE-He213)s10822-017-0034-5-p DE-627 ger DE-627 rakwb eng 570 VZ 12 15,3 ssgn PHARM DE-84 fid BIODIV DE-30 fid Fernández, D. verfasserin aut New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier © Springer International Publishing AG 2017 Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. Inhibitors Second-generation bisphosphonates Human farnesyl pyrophosphate synthase Molecular dynamics Binding free energy Ramis, R. aut Ortega-Castro, J. aut Casasnovas, R. aut Vilanova, B. aut Frau, J. aut Enthalten in Journal of computer aided molecular design Springer International Publishing, 1987 31(2017), 7 vom: 19. Juni, Seite 675-688 (DE-627)130644110 (DE-600)808166-9 (DE-576)018278221 0920-654X nnns volume:31 year:2017 number:7 day:19 month:06 pages:675-688 https://doi.org/10.1007/s10822-017-0034-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-PHARM FID-BIODIV SSG-OLC-MAT SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_70 GBV_ILN_2219 GBV_ILN_4012 AR 31 2017 7 19 06 675-688 |
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10.1007/s10822-017-0034-5 doi (DE-627)OLC2034743512 (DE-He213)s10822-017-0034-5-p DE-627 ger DE-627 rakwb eng 570 VZ 12 15,3 ssgn PHARM DE-84 fid BIODIV DE-30 fid Fernández, D. verfasserin aut New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier © Springer International Publishing AG 2017 Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. Inhibitors Second-generation bisphosphonates Human farnesyl pyrophosphate synthase Molecular dynamics Binding free energy Ramis, R. aut Ortega-Castro, J. aut Casasnovas, R. aut Vilanova, B. aut Frau, J. aut Enthalten in Journal of computer aided molecular design Springer International Publishing, 1987 31(2017), 7 vom: 19. Juni, Seite 675-688 (DE-627)130644110 (DE-600)808166-9 (DE-576)018278221 0920-654X nnns volume:31 year:2017 number:7 day:19 month:06 pages:675-688 https://doi.org/10.1007/s10822-017-0034-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-PHARM FID-BIODIV SSG-OLC-MAT SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_70 GBV_ILN_2219 GBV_ILN_4012 AR 31 2017 7 19 06 675-688 |
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Fernández, D. ddc 570 ssgn 12 fid PHARM fid BIODIV misc Inhibitors misc Second-generation bisphosphonates misc Human farnesyl pyrophosphate synthase misc Molecular dynamics misc Binding free energy New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs |
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570 VZ 12 15,3 ssgn PHARM DE-84 fid BIODIV DE-30 fid New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs Inhibitors Second-generation bisphosphonates Human farnesyl pyrophosphate synthase Molecular dynamics Binding free energy |
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New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs |
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New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs |
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Fernández, D. Ramis, R. Ortega-Castro, J. Casasnovas, R. Vilanova, B. Frau, J. |
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new insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs |
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New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs |
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Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. © Springer International Publishing AG 2017 |
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Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. © Springer International Publishing AG 2017 |
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Abstract Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final $ IC_{50} $ values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the $ R_{2} $ side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar $ IC_{50} $ values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal $ mol^{−1} $ energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity. © Springer International Publishing AG 2017 |
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New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs |
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