更新于：2024-11-01

H1 receptor x α1A-AR

更新于：2024-11-01

基本信息

关联

项与 H1 receptor x α1A-AR 相关的药物

Oxymetazoline Hydrochloride/Chlorpheniramine Maleate

盐酸羟甲唑啉/马来酸氯苯那敏

靶点

H1 receptor x α1A-AR

作用机制

H1 receptor拮抗剂 [+1]

在研机构

CMG Pharmaceutical Co., Ltd.

原研机构

CMG Pharmaceutical Co., Ltd.

在研适应症

普通感冒 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

韩国

首次获批日期2024-09-02

Oxymetazoline Hydrochloride/Chlorpheniramine Maleate/Glycyrrhizinate dipotassium

盐酸羟甲唑啉/马来酸氯苯那敏/甘草酸二钾

靶点

11β-HSD1 x H1 receptor x α1A-AR

作用机制

11β-HSD1抑制剂 [+2]

在研机构

Daewoong Pharmaceutical Co., Ltd.

原研机构

Daewoong Pharmaceutical Co., Ltd.

在研适应症

普通感冒 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

韩国

首次获批日期2024-08-07

100 项与 H1 receptor x α1A-AR 相关的临床结果

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100 项与 H1 receptor x α1A-AR 相关的转化医学

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0 项与 H1 receptor x α1A-AR 相关的专利（医药）

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项与 H1 receptor x α1A-AR 相关的文献（医药）

2024-01-22·Journal of Biomolecular Structure and Dynamics

Tracing the pathways and mechanisms involved in the anti-breast cancer activity of glycyrrhizin using bioinformatics tools and computational methods

Article

作者: Hashemipour, Hassan ; Poustforoosh, Alireza ; Faramarz, Sanaz ; Tüzün, Burak ; Negahdaripour, Manica

A complete investigation to understand the pathways that could be affected by glycyrrhizin (licorice), as anti-breast cancer (BC) agent, has not been performed to date. This study aims to investigate the pathways involved in the anti-cancer activity of glycyrrhizin against BC. For this purpose, the target genes of glycyrrhizin were obtained from the ChEMBL database. The BC-associated genes for three types of BC (breast carcinoma, malignant neoplasm of breast, and triple-negative breast neoplasms) were retrieved from DisGeNET. The target genes of glycyrrhizin and the BC-associated genes were compared, and the genes with disease specificity index (DSI) > 0.6 were selected for further evaluation using in silico methods. The protein-protein interaction (PPI) network was constructed, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. The potential complexes were further evaluated using molecular dynamics (MD) simulation. The results revealed that among 80 common genes, ten genes had DSI greater than 0.6, which included POLK, TACR2, MC3R, TBXAS1, HH1R, SLCO4A1, NPY2R, ADRA2C, ADRA1A, and SLCO2B1. The binding affinity of glycyrrhizin to the cognate proteins and binding characteristics were assessed using molecular docking and binding free energy calculations (MM/GBSA). POLK, TBXAS1, and ADRA1A showed the highest binding affinity with -8.9, -9.3, and -9.6 kcal/mol, respectively. The final targets had an association with BC at several stages of tumor growth. By affecting these targets, glycyrrhizin could influence and control BC efficiently. MD simulation suggested the pathways triggered by the complex glycyrrhizin-ADRA1A were more likely to happen.Communicated by Ramaswamy H. Sarma.

2021-04-01·British Journal of Dermatology1区 · 医学

An additional drug repurposing study for hidradenitis suppurativa/acne inversa

1区 · 医学

Letter

作者: Readhead, B. ; Dudley, J.T. ; Zouboulis, C.C.

Current transcriptome and proteome studies have identified differentially regulated genes and proteins in hidradenitis suppurativa/acne inversa (HS), both in entire involved skin and in involved skin apocrine glands.In this report, we provide addnl. information obtained by further anal. of our data using mol. drug information available through chemogenomic studies.Raw microarray profiles from our own previous studies downloaded from Gene Expression Omnibus (GSE137141) and (GSE144801) were used in this study.The data for anal. originated from whole lesional skin (LS) and nonlesional skin (NLS) of 28 European patients [20 female, eight male; aged 35.0 (10.2) years] with active HS Hurley stage II-III and healthy skin (CS) of 12 matched controls [aged 37.1 (13.2) years].The comparison of LS vs. NLS revealed several new drug target genes, namely ABAT, ADH1C, ADIRF, ADRA1A, ANDR, CFD, CHRM1, CLEC3B, CP3A4, DACB, DRD1, DRD5, GABBR1, GBP6, GBRA6, GBRR1, GCR, GPD1, GRIA1, GRM4, HRH1, IF4H, KRT6B, LPA, MCR, MRCA, MRCB, OPRD, OPRM, PA24A, PBPC, PLAT, PLG, PRKAB1, PTGS1, PTGS2, RPL38, SLC6A4, TA2R, TBXA2R, THAS, TLR2 and UTS2, in addition to the ones detected as HS biomarkers in our previous study, namely DEFB4A/ DEFB4B, GJB2, KRT6A, KRT16, MMP1, MMP9, PI3, S100A7A, S100A8, S100A9, S100A12, SERPINB3, SERPINB4 and SPRR3.Therefore, repurposing drugs may become future targets of investigator-initiated studies supported from peer-reviewed public funding sources.

2019-01-01·Progress in Neuro-Psychopharmacology and Biological Psychiatry2区 · 医学

The effects of single-dose injections of modafinil and methamphetamine on epigenetic and functional markers in the mouse medial prefrontal cortex: potential role of dopamine receptors

2区 · 医学

Article

作者: Sosa, Máximo H ; Bisagno, Verónica ; García-Rill, Edgar ; Urbano, Francisco J ; González, Betina ; Bernardi, Alejandra ; Jayanthi, Subramaniam ; Cadet, Jean-Lud ; Gomez, Natalia ; Torres, Oscar V

METH use causes neuroadaptations that negatively impact the prefrontal cortex (PFC) leading to addiction and associated cognitive decline in animals and humans. In contrast, modafinil enhances cognition by increasing PFC function. Accumulated evidence indicates that psychostimulant drugs, including modafinil and METH, regulate gene expression via epigenetic modifications. In this study, we measured the effects of single-dose injections of modafinil and METH on the protein levels of acetylated histone H3 (H3ac) and H4ac, deacetylases HDAC1 and HDAC2, and of the NMDA subunit GluN1 in the medial PFC (mPFC) of mice euthanized 1 h after drug administration. To test if dopamine (DA) receptors (DRs) participate in the biochemical effects of the two drugs, we injected the D1Rs antagonist, SCH23390, or the D2Rs antagonist, raclopride, 30 min before administration of METH and modafinil. We evaluated each drug effect on glutamate synaptic transmission in D1R-expressing layer V pyramidal neurons. We also measured the enrichment of H3ac and H4ac at the promoters of several genes including DA, NE, orexin, histamine, and glutamate receptors, and their mRNA expression, since they are responsive to chronic modafinil and METH treatment. Acute modafinil and METH injections caused similar effects on total histone acetylation, increasing H3ac and decreasing H4ac, and they also increased HDAC1, HDAC2 and GluN1 protein levels in the mouse mPFC. In addition, the effects of the drugs were prevented by pre-treatment with D1Rs and D2Rs antagonists. Specifically, the changes in H4ac, HDAC2, and GluN1 were responsive to SCH23390, whereas those of H3ac and GluN1 were responsive to raclopride. Whole-cell patch clamp in transgenic BAC-Drd1a-tdTomato mice showed that METH, but not modafinil, induced paired-pulse facilitation of EPSCs, suggesting reduced presynaptic probability of glutamate release onto layer V pyramidal neurons. Analysis of histone 3/4 enrichment at specific promoters revealed: i) distinct effects of the drugs on histone 3 acetylation, with modafinil increasing H3ac at Drd1 and Adra1b promoters, but METH increasing H3ac at Adra1a; ii) distinct effects on histone 4 acetylation enrichment, with modafinil increasing H4ac at the Drd2 promoter and decreasing it at Hrh1, but METH increasing H4ac at Drd1; iii) comparable effects of both psychostimulants, increasing H3ac at Drd2, Hcrtr1, and Hrh1 promoters, decreasing H3ac at Hrh3, increasing H4ac at Hcrtr1, and decreasing H4ac at Hcrtr2, Hrh3, and Grin1 promoters. Interestingly, only METH altered mRNA levels of genes with altered histone acetylation status, inducing increased expression of Drd1a, Adra1a, Hcrtr1, and Hrh1, and decreasing Grin1. Our study suggests that although acute METH and modafinil can both increase DA neurotransmission in the mPFC, there are similar and contrasting epigenetic and transcriptional consequences that may account for their divergent clinical effects.