A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays.
The drug molecule PTC124 (Ataluren) has been described as a read-through agent, capable of suppressing premature termination codons (PTCs) and restoring functional protein production from genes disrupted by nonsense mutations. Following the discovery of PTC124 there was some controversy regarding it...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.1001593 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332429136855040 |
|---|---|
| author | Stuart P McElroy Toshifumi Nomura Leah S Torrie Emma Warbrick Ulrike Gartner Gavin Wood W H Irwin McLean |
| author_facet | Stuart P McElroy Toshifumi Nomura Leah S Torrie Emma Warbrick Ulrike Gartner Gavin Wood W H Irwin McLean |
| author_sort | Stuart P McElroy |
| collection | DOAJ |
| description | The drug molecule PTC124 (Ataluren) has been described as a read-through agent, capable of suppressing premature termination codons (PTCs) and restoring functional protein production from genes disrupted by nonsense mutations. Following the discovery of PTC124 there was some controversy regarding its mechanism of action with two reports attributing its activity to an off-target effect on the Firefly luciferase (FLuc) reporter used in the development of the molecule. Despite questions remaining as to its mechanism of action, development of PTC124 continued into the clinic and it is being actively pursued as a potential nonsense mutation therapy. To thoroughly test the ability of PTC124 to read through nonsense mutations, we conducted a detailed assessment comparing the efficacy of PTC124 with the classical aminoglycoside antibiotic read-through agent geneticin (G418) across a diverse range of in vitro reporter assays. We can confirm the off-target FLuc activity of PTC124 but found that, while G418 exhibits varying activity in every read-through assay, there is no evidence of activity for PTC124. |
| format | Article |
| id | doaj-art-71bb01af95ae43f989b1c9563f2c3741 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-71bb01af95ae43f989b1c9563f2c37412025-08-20T03:46:12ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852013-01-01116e100159310.1371/journal.pbio.1001593A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays.Stuart P McElroyToshifumi NomuraLeah S TorrieEmma WarbrickUlrike GartnerGavin WoodW H Irwin McLeanThe drug molecule PTC124 (Ataluren) has been described as a read-through agent, capable of suppressing premature termination codons (PTCs) and restoring functional protein production from genes disrupted by nonsense mutations. Following the discovery of PTC124 there was some controversy regarding its mechanism of action with two reports attributing its activity to an off-target effect on the Firefly luciferase (FLuc) reporter used in the development of the molecule. Despite questions remaining as to its mechanism of action, development of PTC124 continued into the clinic and it is being actively pursued as a potential nonsense mutation therapy. To thoroughly test the ability of PTC124 to read through nonsense mutations, we conducted a detailed assessment comparing the efficacy of PTC124 with the classical aminoglycoside antibiotic read-through agent geneticin (G418) across a diverse range of in vitro reporter assays. We can confirm the off-target FLuc activity of PTC124 but found that, while G418 exhibits varying activity in every read-through assay, there is no evidence of activity for PTC124.https://doi.org/10.1371/journal.pbio.1001593 |
| spellingShingle | Stuart P McElroy Toshifumi Nomura Leah S Torrie Emma Warbrick Ulrike Gartner Gavin Wood W H Irwin McLean A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. PLoS Biology |
| title | A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. |
| title_full | A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. |
| title_fullStr | A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. |
| title_full_unstemmed | A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. |
| title_short | A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. |
| title_sort | lack of premature termination codon read through efficacy of ptc124 ataluren in a diverse array of reporter assays |
| url | https://doi.org/10.1371/journal.pbio.1001593 |
| work_keys_str_mv | AT stuartpmcelroy alackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT toshifuminomura alackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT leahstorrie alackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT emmawarbrick alackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT ulrikegartner alackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT gavinwood alackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT whirwinmclean alackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT stuartpmcelroy lackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT toshifuminomura lackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT leahstorrie lackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT emmawarbrick lackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT ulrikegartner lackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT gavinwood lackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays AT whirwinmclean lackofprematureterminationcodonreadthroughefficacyofptc124atalureninadiversearrayofreporterassays |