A Phase I, Randomized, Double-blind, Placebo-controlled, Single-Ascending-Dose (SAD) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) of XG2002 Oral Administration in Healthy Adult Volunteers

开始日期2024-04-15

申办/合作机构

Avance Clinical Pty Ltd.初创企业

100 项与 RQ-00434739 相关的临床结果

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100 项与 RQ-00434739 相关的转化医学

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100 项与 RQ-00434739 相关的专利（医药）

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项与 RQ-00434739 相关的文献（医药）

2021-07-01·Journal of Ethnopharmacology2区 · 医学

In silico analysis of the potential mechanism of a preventive Chinese medicine formula on coronavirus disease 2019

2区 · 医学

Article

作者: Qin, You ; Li, Liang ; Yang, Jingjing ; Zhang, Shiying ; Yang, Ping ; Xie, Mengzhou ; Yuan, Zhiying ; Gong, Ke ; Xia, Shuaishuai ; Wu, Huaying

ETHNOPHARMACOLOGICAL RELEVANCEWith the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19.AIM OF THE STUDYTo explore the potential preventive mechanisms of XG-1 against COVID-19 in the combination of network pharmacology approach, single-cell RNA expression profiling analysis, molecular docking and retrospective study.MATERIALS AND METHODSEncyclopedia of Traditional Chinese Medicine (ETCM) database was used to determine the meridian tropism, active components and target genes of XG-1. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were conducted by R Cluster Profiler package (3.14.3). Single cell RNA sequencing (scRNA-seq) data of human lung (GSE122960) was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R Seurat package (3.1.2). Cytoscape (3.7.2) was used to construct the interaction network. The main ingredients in XG-1 were identified by HPLC- Q-TOF- MS and used for molecular docking with COVID-19 3CL hydrolytic enzyme and angiotensin converting enzyme II (ACE2). A retrospective study of 47 close contact participants from Dongtang Community of Hunan Province was conducted to evaluated the preventive effect of XG-1.RESULTSAccording to the network pharmacology analysis, XG-1 formula was closely related to lung-, spleen- and stomach-meridians and include a total of 206 active components and 853 target genes. GO and KEGG pathway enrichment revealed that XG-1 mainly regulated cellular amino acid metabolism process and neuroactive ligand-receptors interaction. The scRNA-seq profiling showed that angiotensin converting enzyme 2 (ACE2) was principally expressed in alveolar type 2 epithelial cells (AT2). 153 genes were up-regulated in AT2 cells expressing ACE2 and 12 genes were obtained by intersecting with XG-1 target genes, of which 3 were related to immunity. Five main chemical ingredients were detected in XG-1 sample by HPLC-Q-TOF-MS. The molecular docking showed that Rutin, Liquiritin and Astragaloside Ⅳ had a good affinity with COVID-19 3CL hydrolytic enzyme and ACE2. Compared with participants who didn't take XG-1, preventive treatment with XG-1gradules resulted in a significant lower rate of testing positive for SARS-CoV-2 nucleic acid (P < 0.0001).CONCLUSIONThe present study showed that XG-1 exerts a preventive effect in close contacts against COVID-19. The underlying mechanism may be related to modulate immunity response through multiple components, pathways, and several target genes co-expressed with ACE2. These findings provide preliminary evidences and methodological reference for the potential preventive mechanism of XG-1 against COVID-19.

2019-02-01·Life Sciences3区 · 医学

RQ-00434739, a novel TRPM8 antagonist, inhibits prostaglandin E2-induced hyperactivity of the primary bladder afferent nerves in rats

3区 · 医学

Article

作者: Homma, Yukio ; Ohshiro, Hiroyuki ; Igawa, Yasuhiko ; Aizawa, Naoki ; Kume, Haruki ; Watanabe, Shuzo

AIMSTo examine the effects of RQ-00434739, a novel selective TRPM8 antagonist, on deep body temperature (DBT) and normal bladder sensory function and overactivity and its associated facilitation of mechanosensitive primary bladder single-unit afferent activities (SAAs) induced by intravesical l-menthol or prostaglandin E2 (PGE2) instillation in rats.MAIN METHODSThe effect of RQ-00434739 on DBT was evaluated using intravenous administration of RQ-00434739 (1 mg/kg) or its vehicle under urethane anaesthesia. Cystometry (CMG) was performed on conscious and freely moving rats. SAAs were measured from the left L6 dorsal root under urethane anaesthesia, and the fibers were grouped as Aδ- or C-fiber based on their conduction velocity. For both CMG and SAA measurements, after baseline recording with saline instillation, further recording was performed with intravesical l-menthol (6 mM) or PGE2 (60 μM) instillation after pretreatment with intravenous RQ-00434739 (1 mg/kg) or its vehicle.KEY FINDINGSRQ-00434739 did not significantly affect DBT. In CMG measurements, RQ-00434739 administration increased mean voided volume. Both l-menthol and PGE2 instillation decreased mean voided volume following vehicle pretreatment, whereas such effects were not observed following RQ-00434739 pretreatment. In SAA measurements, either l-menthol or PGE2 instillations increased SAAs of C-fibers, but not SAAs of Aδ-fibers, in the presence of vehicle. RQ-00434739 pretreatment significantly inhibited the l-menthol- and PGE2-induced activation of C-fiber SAAs.SIGNIFICANCEThe present results demonstrate that blockade of TRPM8 channels can inhibit the pathological activation of mechanosensitive C-fibers and suggest that RQ-00434739 may be a promising therapeutic drug candidate for bladder hypersensitive disorders without affecting DBT.

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适应症	最高研发状态	国家/地区	公司	日期
炎症	临床3期	日本	RaQualia Pharma, Inc.	-
慢性疼痛	临床1期	澳大利亚	RaQualia Pharma, Inc.	-
头痛	临床前	中国	昌郁医药（上海）有限公司	2022-10-12
骨痛	临床前	中国	昌郁医药（上海）有限公司	2022-10-12