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Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2.
PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738205/ https://www.ncbi.nlm.nih.gov/pubmed/33305659 http://dx.doi.org/10.1080/15384101.2020.1859752 |
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author | Theise, Neil D. Arment, Anthony R. Chakravarty, Dimple Gregg, John M. H. Jacobson, Ira M. Jung, Kie Hoon Nair, Sujit S. Tewari, Ashutosh K. Thurston, Archie W. Van Drie, John Westover, Jonna B. |
author_facet | Theise, Neil D. Arment, Anthony R. Chakravarty, Dimple Gregg, John M. H. Jacobson, Ira M. Jung, Kie Hoon Nair, Sujit S. Tewari, Ashutosh K. Thurston, Archie W. Van Drie, John Westover, Jonna B. |
author_sort | Theise, Neil D. |
collection | PubMed |
description | PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.55 µM. PT150 is a member of an extended platform of novel glucocorticoid receptor (GR) and androgen receptor (AR) modulating molecules. In vivo, their predominant net effect is one of systemic glucocorticoid antagonism, but they also show direct downregulation of AR and minor GR agonism at the cellular level. We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol. |
format | Online Article Text |
id | pubmed-7738205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-77382052020-12-16 Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. Theise, Neil D. Arment, Anthony R. Chakravarty, Dimple Gregg, John M. H. Jacobson, Ira M. Jung, Kie Hoon Nair, Sujit S. Tewari, Ashutosh K. Thurston, Archie W. Van Drie, John Westover, Jonna B. Cell Cycle Research Paper PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.55 µM. PT150 is a member of an extended platform of novel glucocorticoid receptor (GR) and androgen receptor (AR) modulating molecules. In vivo, their predominant net effect is one of systemic glucocorticoid antagonism, but they also show direct downregulation of AR and minor GR agonism at the cellular level. We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol. Taylor & Francis 2020-12-11 /pmc/articles/PMC7738205/ /pubmed/33305659 http://dx.doi.org/10.1080/15384101.2020.1859752 Text en © 2020 Informa UK Limited, trading as Taylor & Francis Group |
spellingShingle | Research Paper Theise, Neil D. Arment, Anthony R. Chakravarty, Dimple Gregg, John M. H. Jacobson, Ira M. Jung, Kie Hoon Nair, Sujit S. Tewari, Ashutosh K. Thurston, Archie W. Van Drie, John Westover, Jonna B. Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. |
title | Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. |
title_full | Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. |
title_fullStr | Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. |
title_full_unstemmed | Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. |
title_short | Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2. |
title_sort | clinical stage molecule pt150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against sars-cov-2. |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738205/ https://www.ncbi.nlm.nih.gov/pubmed/33305659 http://dx.doi.org/10.1080/15384101.2020.1859752 |
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