概要基本信息药物类型化学药别名D 21663、D-21663、RC 3095靶点GRPR作用方式拮抗剂作用机制GRPR拮抗剂(胃泌素释放肽前体受体拮抗剂)治疗领域肿瘤呼吸系统疾病泌尿生殖系统疾病在研适应症-非在研适应症肿瘤前列腺癌小细胞肺癌+ [1]原研机构Tulane University Hospital & Clinic在研机构-非在研机构AEterna Zentaris GmbHTulane University Hospital & ClinicÆterna Zentaris, Inc.权益机构-最高研发阶段终止临床2期首次获批日期-最高研发阶段(中国)-特殊审评-登录后查看时间轴结构/序列分子式C56H79N15O9InChIKeyIUYCRRDHLJIJBB-QAGBKCHLSA-NCAS号138147-78-1 Sequence Code 13890089关联100 项与 RC-3095 相关的临床结果登录后查看更多信息100 项与 RC-3095 相关的转化医学登录后查看更多信息100 项与 RC-3095 相关的专利（医药）登录后查看更多信息136 项与 RC-3095 相关的文献（医药）2024-11-01·INFLAMMATION RESEARCHGastrin-releasing peptide receptor antagonist RC-3095 inhibits Porphyromonas gingivalis lipopolysaccharide-accelerated atherosclerosis by suppressing inflammatory responses in endothelial cells and macrophagesArticle作者: Kim, Mi-Kyoung ; Park, Hyun-Joo ; Bae, Moon-Kyoung ; Bae, Soo-Kyung ; Park, Hae Ryoun ; Kim, Yeon ; Kim, Hyung Joon OBJECTIVE:Porphyromonas gingivalis (P. gingivalis), one of the major periodontopathogens, is associated with the progression and exacerbation of atherosclerosis. In this study, we aimed to investigate whether the gastrin-releasing peptide receptor antagonist, RC-3095, could attenuate P. gingivalis LPS-induced inflammatory responses in endothelial cells and macrophages, as well as atherosclerosis in an ApoE-/- mouse model treated with P. gingivalis LPS.METHODS:The effect of RC-3095 on P. gingivalis LPS-induced endothelial inflammation was examined using HUVECs and rat aortic endothelium. THP-1 cells were polarized into M1 macrophages by exposure to P. gingivalis LPS, with or without RC-3095. The effect of RC-3095 on atherosclerosis progression was assessed in high-fat-fed male ApoE-/- mice through injections of P. gingivalis LPS, RC-3095, or a combination of both.RESULTS:RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells and aortic endothelium by suppressing NF-κB-dependent expressions of ICAM-1 and VCAM-1. In addition, RC-3095 inhibited the P. gingivalis LPS-induced polarization of M1 macrophages by blocking the MAPK and NF-κB signaling pathways. Moreover, RC-3095 decreased the area of atherosclerotic lesions in ApoE-/- mice, which was accelerated by P. gingivalis LPS injection, and lowered the expressions of ICAM-1 and VCAM-1 in the aortic tissue of mice with atherosclerosis.CONCLUSIONS:RC-3095 can alleviate P. gingivalis LPS-induced endothelial inflammation, macrophage polarization, and atherosclerosis progression, suggesting its potential as a therapeutic approach for periodontal pathogen-associated atherosclerosis.2024-04-18·Alternative therapies in health and medicineGastrin-Releasing Peptide/Gastrin-Releasing Peptide Receptor Participation in Itch Sensation Signaling in the Spinal Cord of Uremic Pruritus Mice.Article作者: Li, Huili ; Chen, Hao ; Wang, Yitong ; Zhang, Ze ; Du, Liang ; Gao, Weiwei Background:Uremic pruritus is a prevalent clinical symptom in maintenance dialysis patients. Existing evidence establishes a connection between itch transmission and the gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway.Objective:To investigate the involvement of the gastrin-releasing peptide/gastrin-releasing peptide receptor in itch sensation signaling within the spinal cord of uremic pruritus.Design:An animal study was conducted.Setting:The research was conducted at the First Hospital of Hebei Medical University.Participants:A total of 50 male C57BL/6J mice (weight: 30-40 g) were acquired from Beijing Weitonglihua Laboratory Animal Center.Interventions:Mice were categorized into five groups: normal, sham, Y, A, and B. The Y group received intrathecal injections of saline (5 ul). The A group received intrathecal injections of gastrin-releasing peptide (0.1 nmol, 5 ul), and the B group received intrathecal injections of the gastrin-releasing peptide receptor antagonist RC-3095 (0.3 mmol, 5 ul).Primary Outcome Measures:(1) Pruritus behavior of mice and (2) expression of gastrin-releasing peptide, gastrin-releasing peptide receptor, and inositol trisphosphate.Results:Scratching times in the Y group significantly surpassed those of normal and sham groups, increasing over time. Gastrin-releasing peptide and receptor expression rose in the uremic pruritus mouse model compared to normal and sham groups (P < .05). Expression of gastrin-releasing peptide and its receptor was significantly elevated in the uremic pruritus mouse model compared to the normal and sham groups (P < .05). Inositol trisphosphate expression in the dorsal spinal horn of Y group mice increased compared to normal and sham groups. Intrathecal gastrin-releasing peptide heightened inositol trisphosphate expression, while the peptide receptor antagonist RC-3095 reduced it. Y group scratching times were higher than normal and sham groups, increasing after intrathecal gastrin-releasing peptide but decreasing after RC-3095 injection.Conclusion:The gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway is involved in the development of uremic pruritus.2022-04-01·Biochemical pharmacology2区 · 医学Functional roles of neuromedin B and gastrin-releasing peptide in regulating itch and pain in the spinal cord of non-human primates2区 · 医学Article作者: Peters, Christopher M ; Ding, Huiping ; Mabry, Kelsey M ; Park, Sun H ; Kiguchi, Norikazu ; Ko, Mei-Chuan ; Shiozawa, Yusuke ; Alfonso Romero-Sandoval, E ; Kishioka, Shiroh Despite accumulating evidence in rodents, the functional role of neuromedin B (NMB) in regulating somatosensory systems in primate spinal cord is unknown. We aimed to compare the expression patterns of NMB and its receptor (NMBR) and the behavioral effects of intrathecal (i.t.) NMB with gastrin-releasing peptide (GRP) on itch or pain in non-human primates (NHPs). We used six adult rhesus monkeys. The mRNA or protein expressions of NMB, GRP, and their receptors were evaluated by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, or in situ hybridization. We determined the behavioral effects of NMB or GRP via acute thermal nociception, capsaicin-induced thermal allodynia, and itch scratching response assays. NMB expression levels were greater than those of GRP in the dorsal root ganglia and spinal dorsal horn. Conversely, NMBR expression was significantly lower than GRP receptor (GRPR). I.t. NMB elicited only mild scratching responses, whereas GRP caused robust scratching responses. GRP- and NMB-elicited scratching responses were attenuated by GRPR (RC-3095) and NMBR (PD168368) antagonists, respectively. Moreover, i.t. NMB and GRP did not induce thermal hypersensitivity and GRPR and NMBR antagonists did not affect peripherally elicited thermal allodynia. Consistently, NMBR expression was low in both itch- and pain-responsive neurons in the spinal dorsal horn. Spinal NMB-NMBR system plays a minimal functional role in the neurotransmission of itch and pain in primates. Unlike the functional significance of the GRP-GRPR system in itch, drugs targeting the spinal NMB-NMBR system may not effectively alleviate non-NMBR-mediated itch.100 项与 RC-3095 相关的药物交易登录后查看更多信息研发状态10 条进展最快的记录, 登录 后查看更多信息适应症最高研发状态国家/地区公司日期肿瘤临床2期美国 Æterna Zentaris, Inc.-前列腺癌临床2期-Tulane University Hospital & Clinic-前列腺癌临床2期-AEterna Zentaris GmbH-小细胞肺癌临床2期-AEterna Zentaris GmbH-小细胞肺癌临床2期-Tulane University Hospital & Clinic-实体瘤临床1期巴西 Æterna Zentaris, Inc.-登录后查看更多信息临床结果适应症分期评价查看全部结果研究分期人群特征评价人数分组结果评价发布日期 No Data

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