更新于：2024-11-01

PDE10A x A2aR

更新于：2024-11-01

基本信息

关联

项与 PDE10A x A2aR 相关的药物

PBF-999

靶点

A2aR x PDE10A

作用机制

A2aR拮抗剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 PDE10A x A2aR 相关的临床试验

CTIS2022-501462-22-00 / RecruitingIIT

A Phase 2 Study to Evaluate Efficacy, Safety, and Pharmacokinetics of PBF-999 in the Treatment of Patients with Prader-Willi Syndrome. - PBF-999CT-04

开始日期2023-03-14

申办/合作机构-

NCT03786484 / Completed临床1期

Phase I/Ib Trial of Single Agent PBF-999 in Solid Tumour Advanced Cancer

Multicentric phase I (dose escalation plus expansion) clinical trial of PBF-999 in patients with immunotherapy naïve and pretreated solid tumors to evaluate the safety, tolerability and preliminary efficacy of the compound

开始日期2017-10-01

申办/合作机构

Palobiofarma SL

[+1]

NCT02907294 / Terminated临床1期

Randomized, Double Blind, Placebo Controlled, Parallel Groups Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of PBF-999 (160 mg and 320 mg) "After Multiple Oral Doses" in Healthy Volunteers

To assess the safety and tolerability of five doses of PBF-999 (160 mg and 320mg) after repeated (8 days) single daily oral dose administration in young male and female healthy subjects.

开始日期2016-03-01

申办/合作机构

Palobiofarma SL

100 项与 PDE10A x A2aR 相关的临床结果

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100 项与 PDE10A x A2aR 相关的转化医学

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0 项与 PDE10A x A2aR 相关的专利（医药）

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项与 PDE10A x A2aR 相关的文献（医药）

2022-09-01·Chemical and Pharmaceutical Bulletin

Effects of Long-Term Administration of Q808 on Hippocampal Transcriptome in Healthy Rats

Article

作者: Wu, Di ; Liu, Ning ; Wang, Qing ; Zhang, Dianwen ; Chen, Tianli ; Li, Xiang

Epilepsy treatment with antiepileptic drugs (AEDs) is usually requires for many years. Q808 is an innovative antiepileptic chemical. It exerts effective antiepileptic effect against various epilepsy models. Exploring the gene transcriptomic profile of long-term treatment of Q808 is necessary. In the present study, hippocampus RNA-sequencing was performed to reveal the transcriptome profile of rats before and after treatment of Q808 for 28 d. Results confirmed 51 differentially expressed genes (DEGs) between Q808 and healthy control groups. Gene cluster analysis showed that most upregulated DEGs linked to response to drug and nucleus, most downregulated DEGs linked to locomotory, neuronal cell body, and drug binding. Most of DEGs were enriched in the signaling transduction, substance dependence, nervous system, and neurodegenerative disease pathways. Furthermore, quantitative real-time PCR analysis confirmed that Q808 significantly increased the expression of neuroprotective genes, such as Mdk, and decreased the mRNA levels of Penk, Drd1, and Adora2a, which are highly expressed in epilepsy models. In addition, Q808 decreased the mRNA expression of Pde10A and Drd2, which are known to be closely associated with schizophrenia. Our study may provide a theoretical basis to explore the effect of Q808 on the susceptibility to epilepsy and other neurological diseases.

2021-12-01·Journal of Cheminformatics2区 · 化学

Structure‐based identification of dual ligands at the A2AR and PDE10A with anti‐proliferative effects in lung cancer cell‐lines

2区 · 化学

ArticleOA

作者: Bermudez, Marcel ; Bender, Andreas ; Carvalho, Sabrina ; Ladds, Graham ; Winfield, Ian ; Glen, Robert ; Safitri, Dewi ; Kalash, Leen

AbstractEnhanced/prolonged cAMP signalling has been suggested as a suppressor of cancer proliferation. Interestingly, two key modulators that elevate cAMP, the A2A receptor (A2AR) and phosphodiesterase 10A (PDE10A), are differentially co-expressed in various types of non-small lung cancer (NSCLC) cell-lines. Thus, finding dual-target compounds, which are simultaneously agonists at the A2AR whilst also inhibiting PDE10A, could be a novel anti-proliferative approach. Using ligand- and structure-based modelling combined with MD simulations (which identified Val84 displacement as a novel conformational descriptor of A2AR activation), a series of known PDE10A inhibitors were shown to dock to the orthosteric site of the A2AR. Subsequent in-vitro analysis confirmed that these compounds bind to the A2AR and exhibit dual-activity at both the A2AR and PDE10A. Furthermore, many of the compounds exhibited promising anti-proliferative effects upon NSCLC cell-lines, which directly correlated with the expression of both PDE10A and the A2AR. Thus, we propose a structure-based methodology, which has been validated in in-vitro binding and functional assays, and demonstrated a promising therapeutic value.

2018-09-01·Stroke1区 · 医学

RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke

1区 · 医学

Article

作者: McNab, Jennifer A. ; Ishizaka, Shunsuke ; Zeineh, Michael ; Wang, Eric H. ; Ito, Masaki ; Smerin, Daniel L. ; Aswendt, Markus ; Cheng, Michelle Y. ; Leuze, Christoph ; Goubran, Maged ; Cao, Zhijuan ; Levy, Sabrina L. ; Lee, Alex G. ; Steinberg, Gary K.

Background and Purpose—Many restorative therapies have been used to study brain repair after stroke. These therapeutic-induced changes have revealed important insights on brain repair and recovery mechanisms; however, the intrinsic changes that occur in spontaneously recovery after stroke is less clear. The goal of this study is to elucidate the intrinsic changes in spontaneous recovery after stroke, by directly investigating the transcriptome of primary motor cortex in mice that naturally recovered after stroke.Methods—Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion. Functional recovery was evaluated using the horizontal rotating beam test. A novel in-depth lesion mapping analysis was used to evaluate infarct size and locations. Ipsilesional and contralesional primary motor cortices (iM1 and cM1) were processed for RNA-sequencing transcriptome analysis.Results—Cluster analysis of the stroke mice behavior performance revealed 2 distinct recovery groups: a spontaneously recovered and a nonrecovered group. Both groups showed similar lesion profile, despite their differential recovery outcome. RNA-sequencing transcriptome analysis revealed distinct biological pathways in the spontaneously recovered stroke mice, in both iM1 and cM1. Correlation analysis revealed that 38 genes in the iM1 were significantly correlated with improved recovery, whereas 74 genes were correlated in the cM1. In particular, ingenuity pathway analysis highlighted the involvement of cAMP signaling in the cM1, with selective reduction of Adora2a (adenosine receptor A2A), Drd2 (dopamine receptor D2), and Pde10a (phosphodiesterase 10A) expression in recovered mice. Interestingly, the expressions of these genes in cM1 were negatively correlated with behavioral recovery.Conclusions—Our RNA-sequencing data revealed a panel of recovery-related genes in the motor cortex of spontaneously recovered stroke mice and highlighted the involvement of contralesional cortex in spontaneous recovery, particularly Adora2a, Drd2, and Pde10a-mediated cAMP signaling pathway. Developing drugs targeting these candidates after stroke may provide beneficial recovery outcome.