A Phase 2 Dose Finding Study Evaluating the Safety and Efficacy of Linaclotide in Pediatric Subjects 6 Months to Less Than 2 Years of Age with Functional Constipation (FC). - M21-862

开始日期2024-08-14

申办/合作机构

AbbVie Deutschland GmbH & Co. KG

ChiCTR2400083515 / Recruiting临床4期IIT

Effect of linaclotide combined with compound polyethylene glycol electrolyte powder in bowel preparation before colonoscopy in patients with constipation

开始日期2024-04-29

申办/合作机构

重庆医科大学附属第二医院

ChiCTR2400081524 / Recruiting临床4期IIT

Application of linaclotide in bowel preparation before colonoscopy in patients with constipation

开始日期2024-01-02

申办/合作机构-

100 项与 sGC x GC-C 相关的临床结果

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100 项与 sGC x GC-C 相关的转化医学

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0 项与 sGC x GC-C 相关的专利（医药）

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项与 sGC x GC-C 相关的文献（医药）

2022-01-01·General and Comparative Endocrinology3区 · 医学

Evolution of the membrane/particulate guanylyl cyclase: From physicochemical sensors to hormone receptors

3区 · 医学

Review

作者: Takei, Yoshio

Guanylyl cyclase (GC) is an enzyme that produces 3',5'-cyclic guanosine monophosphate (cGMP), one of the two canonical cyclic nucleotides used as a second messenger for intracellular signal transduction. The GCs are classified into two groups, particulate/membrane GCs (pGC) and soluble/cytosolic GCs (sGC). In relation to the endocrine system, pGCs include hormone receptors for natriuretic peptides (GC-A and GC-B) and guanylin peptides (GC-C), while sGC is a receptor for nitric oxide and carbon monoxide. Comparing the functions of pGCs in eukaryotes, it is apparent that pGCs perceive various environmental factors such as light, temperature, and various external chemical signals in addition to endocrine hormones, and transmit the information into the cell using the intracellular signaling cascade initiated by cGMP, e.g., cGMP-dependent protein kinases, cGMP-sensitive cyclic nucleotide-gated ion channels and cGMP-regulated phosphodiesterases. Among vertebrate pGCs, GC-E and GC-F are localized on retinal epithelia and are involved in modifying signal transduction from the photoreceptor, rhodopsin. GC-D and GC-G are localized in olfactory epithelia and serve as sensors at the extracellular domain for external chemical signals such as odorants and pheromones. GC-G also responds to guanylin peptides in the urine, which alters sensitivity to other chemicals. In addition, guanylin peptides that are secreted into the intestinal lumen, a pseudo-external environment, act on the GC-C on the apical membrane for regulation of epithelial transport. In this context, GC-C and GC-G appear to be in transition from exocrine pheromone receptor to endocrine hormone receptor. The pGCs also exist in various deuterostome and protostome invertebrates, and act as receptors for environmental, exocrine and endocrine factors including hormones. Tracing the evolutionary history of pGCs, it appears that pGCs first appeared as a sensor for physicochemical signals in the environment, and then evolved to function as hormone receptors. In this review, the author proposes an evolutionary history of pGCs that highlights the emerging role of the GC/cGMP system for signal transduction in hormone action.

2012-10-01·Diabetes1区 · 医学

A Cyclic Guanosine Monophosphate–Dependent Pathway Can Regulate Net Hepatic Glucose Uptake in Vivo

1区 · 医学

Article

作者: Smith, Marta ; Winnick, Jason J. ; An, Zhibo ; Farmer, Ben ; Cherrington, Alan D. ; Irimia, Jose M. ; Moore, Mary C. ; Roach, Peter J.

We previously showed that hepatic nitric oxide regulates net hepatic glucose uptake (NHGU), an effect that can be eliminated by inhibiting hepatic soluble guanylate cyclase (sGC), suggesting that the sGC pathway is involved in the regulation of NHGU. The aim of the current study was to determine whether hepatic cyclic guanosine monophosphate (cGMP) reduces NHGU. Studies were performed on conscious dogs with transhepatic catheters. A hyperglycemic-hyperinsulinemic clamp was established in the presence of portal vein glucose infusion. 8-Br-cGMP (50 µg/kg/min) was delivered intraportally, and either the glucose load to the liver (CGMP/GLC; n = 5) or the glucose concentration entering the liver (CGMP/GCC; n = 5) was clamped at 2× basal. In the control group, saline was given intraportally (SAL; n = 10), and the hepatic glucose concentration and load were doubled. 8-Br-cGMP increased portal blood flow, necessitating the two approaches to glucose clamping in the cGMP groups. NHGU (mg/kg/min) was 5.8 ± 0.5, 2.7 ± 0.5, and 4.8 ± 0.3, whereas the fractional extraction of glucose was 11.0 ± 1, 5.5 ± 1, and 8.5 ± 1% during the last hour of the study in SAL, CGMP/GLC, and CGMP/GCC, respectively. The reduction of NHGU in response to 8-Br-cGMP was associated with increased AMP-activated protein kinase phosphorylation. These data indicate that changes in liver cGMP can regulate NHGU under postprandial conditions.

2011-07-01·Basic Research in Cardiology1区 · 医学

Regulation of vascular guanylyl cyclase by endothelial nitric oxide-dependent posttranslational modification

1区 · 医学

Article

作者: Tatsiana Suvorava ; Jens W. Fischer ; Till Freudenberger ; Georg Kojda ; Marc Oppermann ; Vu Thao-Vi Dao ; Martina Weber

In isolated cells, soluble guanylyl cyclase (sGC) activity is regulated by exogenous nitric oxide (NO) via downregulation of expression and posttranslational S-nitrosylation. The aim of this study was to investigate whether such regulatory mechanism impact on endothelium-dependent vasodilation in a newly developed mouse strain carrying an endothelial-specific overexpression of eNOS (eNOS(++)). When compared with transgene negative controls (eNOS(n)), eNOS(++)-mice showed a 3.3-fold higher endothelial-specific aortic eNOS expression, increased vascular cGMP and VASP phosphorylation, a L-nitroarginine (L-NA)-inhibitable decrease in systolic blood pressure, but normal levels of peroxynitrite and nitrotyrosine formation, endothelium-dependent aortic vasodilation and vasodilation to NO donors. Western blot analysis for sGC showed similar protein levels of sGC-α1 and sGC-β1 subunits in eNOS(n) and eNOS(++). In striking contrast, the activity of isolated sGC was strongly decreased in lungs of eNOS(++). Semiquantitative evaluation of sGC-β1-S-nitrosylation demonstrated that this loss of sGC activity is associated with increased nitrosylation of the enzyme in eNOS(++), a difference that disappeared after L-NA-treatment. Our data suggest the existence of a physiologic NO-dependent posttranslational regulation of vascular sGC in mammals involving S-nitrosylation as a key mechanism. Because this mechanism can compensate for reduction in vascular NO bioavailability, it may mask the development of endothelial dysfunction.

项与 sGC x GC-C 相关的新闻（医药）

2022-04-19

·新浪医药新闻

针对实体瘤！斯丹赛生物CAR-T产品获FDA快速通道资格

4月19日，斯丹赛生物宣布，美国FDA已授予GCC19CART快速通道资格。GCC19CART是一种靶向GCC的自体CAR-T治疗产品，为斯丹赛生物开发的用于治疗复发难治转移型结直肠癌（R/R mCRC）的实体肿瘤疗法。公开资料显示，斯丹赛生物专注于开发治疗实体瘤的细胞免疫疗法，其独特的CoupledCAR技术平台旨在克服治疗实体瘤的常见挑战。GCC19CART专门设计用于靶向并清除表达结直肠癌肿瘤标记物GCC的癌细胞。公开资料显示，鸟苷酸环化酶C（GCC/GUCY2C）属于受体鸟苷酸环化酶家族中的一员。近年来研究发现，GCC在原发性结直肠癌细胞中稳定表达，而在转移性结直肠癌细胞中异常高表达，被认为是转移性结直肠癌的特异性标志分子之一。早先，GCC19CART在中国进行的35例R/R mCRC患者的临床试验已取得初步成果。研究者在中国发起的早期临床试验（IRB）中，累计入组35名晚期结直肠癌患者，在剂量爬坡实验中接受了2✖10^6的GCC19CART细胞/千克剂量的8名患者中，观察到了50%的客观缓解率。据悉，FDA正是基于GCC19CART在常规疗法无效的R/R mCRC患者治疗中体现出的潜力，而授予其快速通道资格。GCC19CART已经在去年8月获得FDA的临床试验批件，斯丹赛生物计划于2022年中在美国启动该疗法针对R/R mCRC的1期临床试验。经美国国家综合癌症委员会（NCCN）认定的复发难治型结直肠癌被定义为：经多线标准治疗无效或发展转移的患者，这类患者只有极少的有效治疗选项。而R/R mCRC患者三线治疗的客观缓解率为1%~1.6%，总中位数生存期仅为6.4~7.1个月，存在未被满足的医疗需求。参考资料： [1]高特佳Ecosystem | FDA授予斯丹赛生物肠癌CAR-T治疗产品快速通道资格.Retrieved Apr 19, 2022.From https://mp.weixin.qq.com/s/vvQl7ktLaMUtALazGqHXWg [2]高特佳Ecosystem | 斯丹赛生物完成超4千万美元C轮融资，实体瘤CAR-T获美国IND批准.Retrieved Sep 6, 2021.From https://mp.weixin.qq.com/s/Efu_uXlvKCgcg3wMlKWgBg 内容来源于网络，如有侵权，请联系删除，谢谢。

快速通道免疫疗法细胞疗法