fo3t949n

Property	Value
?:abstract	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 microM 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 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.
is ?:annotates of	<https://research.tib.eu/covid-19/entity/fo3t949n_hasAnnotation_C0003289> <https://research.tib.eu/covid-19/entity/fo3t949n_hasAnnotation_C0042776> <https://research.tib.eu/covid-19/entity/fo3t949n_hasAnnotation_C1336641> <https://research.tib.eu/covid-19/entity/fo3t949n_hasAnnotation_C1422064> <https://research.tib.eu/covid-19/entity/fo3t949n_hasAnnotation_C5203676>
?:creator	<https://research.tib.eu/covid-19/entity/Theise%2C_N._D.%3B_Arment%2C_A._R.%3B_Chakravarty%2C_D.%3B_Gregg%2C_J._M._H.%3B_Jacobson%2C_I._M.%3B_Jung%2C_K._H.%3B_Nair%2C_S._S.%3B_Tewari%2C_A._K.%3B_Thurston%2C_A._W.%3B_Van_Drie%2C_J.%3B_Westover%2C_J._B.> <https://research.tib.eu/covid-19/entity/Theise%2C_Neil_D%3B_Arment%2C_Anthony_R%3B_Chakravarty%2C_Dimple%3B_Gregg%2C_John_M_H%3B_Jacobson%2C_Ira_M%3B_Jung%2C_Kie_Hoon%3B_Nair%2C_Sujit_S%3B_Tewari%2C_Ashutosh_K%3B_Thurston%2C_Archie_W%3B_Van_Drie%2C_John%3B_Westover%2C_Jonna_B>
?:journal	Cell_Cycle
?:license	unk
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
?:source	WHO
?:title	Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:who_covidence_id	#1066164 #33305659 #972592
?:year	2020

Property

Value

?:abstract

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 microM 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
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.

is ?:annotates of