PT-150(PT-150) - 药物靶点：GR_在研适应症：新型冠状病毒感染，抑郁症，酗酒_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

GR

作用机制

GR拮抗剂(糖皮质激素受体拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Pop Test Oncology LLC

Pop Test LLC

非在研机构

Merck Sharp & Dohme Corp.MSD Oss BV

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C28H30O4

InChIKeyDFELGYQKEOCHOA-BZAFBGKRSA-N

CAS号189035-07-2

关联

6

项与 PT-150 相关的临床试验

NCT04331288 / Completed临床1期

PT150 (Formerly ORG34517) as a Potential Treatment for Alcohol Dependence-Alcohol Interaction Study

The purpose of this clinical study is to assess pharmacokinetic interactions between ethanol (EtOH) and PT150 (900 mg qd) in non-treatment-seeking alcohol-experienced volunteers-(to include military service members, veterans and/or civilians).

开始日期2021-11-01

申办/合作机构

Pop Test Oncology LLC

[+3]

NCT03548714 / Completed临床1期

PT150 (Formerly ORG34517) as a Potential Treatment for Alcohol Dependence-Alcohol Interaction Study

The purpose of the clinical study is to compare pharmacodynamic and safety endpoints following an alcohol challenge prior to and concurrent with PT150 (study drug) treatment.

开始日期2018-09-01

申办/合作机构

Pop Test Oncology LLC

[+4]

NCT00844922 / Completed临床2期

Double-blind, Placebo-controlled Trial Investigating the Safety of Re-exposure to 900 mg of Org 34517, Used as Adjunctive Therapy in Subjects With Psychotic Major Depression (Major Depressive Episode, Severe, With Psychotic Features), Who Participated in Trial 28130

Patients who participated in the previous trial 28130, who were eligible, were entered into this trial. Patients who were randomized to placebo in the previous trial 28130 continued on placebo while patients who were randomized to Org 34517 (SCH 900636), regardless of dose, were titrated to 900 mg Org 34517. Patients in this trial took their study medication for 2 weeks in order to study the safety and tolerability of Org 34517.

开始日期2005-09-01

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 PT-150 相关的临床结果

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100 项与 PT-150 相关的转化医学

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100 项与 PT-150 相关的专利（医药）

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19

项与 PT-150 相关的文献（医药）

2024-07-01·NeuroToxicology

Neuroprotective efficacy of the glucocorticoid receptor modulator PT150 in the rotenone mouse model of Parkinson’s disease

Article

作者: Latham, Amanda S ; Rocha, Savannah M ; McDermott, Casey P ; Slayden, Richard A ; Tjalkens, Ronald B ; Reigan, Philip

Parkinson's disease (PD) is the most common neurodegenerative movement disorder worldwide. Current treatments for PD largely center around dopamine replacement therapies and fail to prevent the progression of pathology, underscoring the need for neuroprotective interventions. Approaches that target neuroinflammation, which occurs prior to dopaminergic neuron (DAn) loss in the substantia nigra (SN), represent a promising therapeutic strategy. The glucocorticoid receptor (GR) has been implicated in the neuropathology of PD and modulates numerous neuroinflammatory signaling pathways in the brain. Therefore, we investigated the neuroprotective effects of the novel GR modulator, PT150, in the rotenone mouse model of PD, postulating that inhibition of glial inflammation would protect DAn and reduce accumulation of neurotoxic misfolded ⍺-synuclein protein. C57Bl/6 mice were exposed to 2.5 mg/kg/day rotenone by intraperitoneal injection for 14 days. Upon completion of rotenone dosing, mice were orally treated at day 15 with 30 mg/kg/day or 100 mg/kg/day PT150 in the 14-day post-lesioning incubation period, during which the majority of DAn loss and α-synuclein (α-syn) accumulation occurs. Our results indicate that treatment with PT150 reduced both loss of DAn and microgliosis in the nigrostriatal pathway. Although morphologic features of astrogliosis were not attenuated, PT150 treatment promoted potentially neuroprotective activity in these cells, including increased phagocytosis of hyperphosphorylated α-syn. Ultimately, PT150 treatment reduced the loss of DAn cell bodies in the SN, but not the striatum, and prohibited intra-neuronal accumulation of α-syn. Together, these data indicate that PT150 effectively reduced SN pathology in the rotenone mouse model of PD.

2024-01-01·Molecular Pharmacology

Synergy between Interleukin-1β, Interferon-γ, and Glucocorticoids to Induce TLR2 Expression Involves NF-κB, STAT1, and the Glucocorticoid Receptor

Article

作者: Leigh, Richard ; Newton, Robert ; Gill, Sachman ; Thorne, Andrew ; Kooi, Cora ; Kalyanaraman, Keerthana ; Bansal, Akanksha ; Milani, Arya ; Mostafa, Mahmoud M ; Chandramohan, Priyanka ; Necker-Brown, Amandah

Glucocorticoids act via the glucocorticoid receptor (GR; NR3C1) to downregulate inflammatory gene expression and are effective treatments for mild to moderate asthma. However, in severe asthma and virus-induced exacerbations, glucocorticoid therapies are less efficacious, possibly due to reduced repressive ability and/or the increased expression of proinflammatory genes. In human A549 epithelial and primary human bronchial epithelial cells, toll-like receptor (TLR)-2 mRNA and protein were supra-additively induced by interleukin-1β (IL-1β) plus dexamethasone (IL-1β+Dex), interferon-γ (IFN-γ) plus dexamethasone (IFN-γ+Dex), and IL-1β plus IFN-γ plus dexamethasone (IL-1β+IFN-γ+Dex). Indeed, ∼34- to 2100-fold increases were apparent at 24 hours for IL-1β+IFN-γ+Dex, and this was greater than for any single or dual treatment. Using the A549 cell model, TLR2 induction by IL-1β+IFN-γ+Dex was antagonized by Org34517, a competitive GR antagonist. Further, when combined with IL-1β, IFN-γ, or IL-1β+IFN-γ, the enhancements by dexamethasone on TLR2 expression required GR. Likewise, inhibitor of κB kinase 2 inhibitors reduced IL-1β+IFN-γ+Dex-induced TLR2 expression, and TLR2 expression induced by IL-1β+Dex, with or without IFN-γ, required the nuclear factor (NF)-κB subunit, p65. Similarly, signal transducer and activator of transcription (STAT)-1 phosphorylation and γ-interferon-activated sequence-dependent transcription were induced by IFN-γ These, along with IL-1β+IFN-γ+Dex-induced TLR2 expression, were inhibited by Janus kinase (JAK) inhibitors. As IL-1β+IFN-γ+Dex-induced TLR2 expression also required STAT1, this study reveals cooperation between JAK-STAT1, NF-κB, and GR to upregulate TLR2 expression. Since TLR2 agonism elicits inflammatory responses, we propose that synergies involving TLR2 may occur within the cytokine milieu present in the immunopathology of glucocorticoid-resistant disease, and this could promote glucocorticoid resistance. SIGNIFICANCE STATEMENT: This study highlights that in human pulmonary epithelial cells, glucocorticoids, when combined with the inflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ), can synergistically induce the expression of inflammatory genes, such as TLR2. This effect involved positive combinatorial interactions between NF-κB/p65, glucocorticoid receptor, and JAK-STAT1 signaling to synergistically upregulate TLR2 expression. Thus, synergies involving glucocorticoid enhancement of TLR2 expression may occur in the immunopathology of glucocorticoid-resistant inflammatory diseases, including severe asthma.

2023-02-01·Psychopharmacology

PT150 blocks the rewarding properties of ethanol and attenuates ethanol-induced reduction of egg laying in Coturnix quail

Article

作者: Radevski, Mia E ; Bardo, Michael T ; Prendergast, Mark A ; Akins, Chana K

RATIONALEAlcohol use disorder (AUD) has been shown to be associated with a dysregulated stress system. Reducing the stress hormone corticosterone (CORT), that binds to glucocorticoid receptors, may attenuate the rewarding properties of drugs of abuse. However, the effect of blocking corticosterone receptors on ethanol reward has yet to be investigated.OBJECTIVESThe current study investigated whether the stress hormone receptor antagonist, PT150, would block the rewarding properties of ethanol via the glucocorticoid receptor system and attenuate other ethanol-induced effects.METHODSA conditioned place preference (CPP) procedure was used to examine the rewarding properties of ethanol in an avian preclinical model. Ethanol was paired with the least preferred chamber. On alternate days, water was paired with the preferred chamber. After eight pairings, a place preference test was given that allowed subjects to have access to both chambers. Half of the subjects received PT150 prior to ethanol administration. The other half received vehicle. Time spent in each chamber during the preference tests, locomotor activity during the pairings, and egg production in female birds was recorded.RESULTSEthanol treatment resulted in a CPP and pretreatment of PT150 blocked the acquisition of the ethanol-induced place preference. Neither ethanol nor PT150 altered locomotor activity. Pretreatment of PT150 also increased egg production in female quail treated with ethanol.CONCLUSIONSThese findings suggest repeated ethanol pairings with visual cues can produce a CPP. Furthermore, pretreatment of PT150 may be a potential pharmacotherapy for blocking the rewarding properties of ethanol and may enhance egg production in female quail treated with ethanol.

100 项与 PT-150 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05423

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床2期	美国	Pop Test LLC	2022-01-30
精神障碍	临床1期	-	Merck Sharp & Dohme Corp.	2004-07-01
抑郁症	临床1期	美国	MSD Oss BV	2000-11-01
酗酒	临床1期	美国	Pop Test LLC	-
乳腺癌	临床1期	-	Merck Sharp & Dohme Corp.	-
重度抑郁症	临床1期	欧洲	-	-
重度抑郁症	临床1期	美国	-	-
乳腺癌	药物发现	-	Merck Sharp & Dohme Corp.	-
重度抑郁症	药物发现	美国	-	-
重度抑郁症	药物发现	欧洲	-	-