更新于：2024-11-01

RET x GFRα3

更新于：2024-11-01

基本信息

关联

项与 RET x GFRα3 相关的药物

GFRα/RET receptor agonist (GeneCode)

靶点

GFRα3 x RET

作用机制

GFRα3 agonists [+1]

在研机构

GeneCode Ltd.

原研机构

GeneCode Ltd.

在研适应症

帕金森病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 RET x GFRα3 相关的临床结果

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100 项与 RET x GFRα3 相关的转化医学

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0 项与 RET x GFRα3 相关的专利（医药）

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项与 RET x GFRα3 相关的文献（医药）

2024-09-01·Bioorganic & Medicinal Chemistry Letters

Discovery of the first selective, small-molecule GFRα2/3 inhibitors through DNA-encoded library technology

Article

作者: Missig, Galen ; Nguyen, Hanh Nho ; Ho, Tammy Szu-Yu ; Johnson, Shea L ; Choi-Sledeski, Yong Mi ; Lim, Jongwon ; Pin, Sokhom ; Toh, May Fern ; Gray, David ; Gupta, Kushali ; Ouk, Kosalvisal ; Wang, Minghua ; Stone, David J ; Barberis, Claude ; Zhang, Hongjun

Studies have shown that disrupting the formation of the ligand-RET-GFRα complex could be an effective way of treating pain and itch. Compared to traditional high-throughput screens, DNA encoded libraries (DELs) have distinguished themselves as a powerful technology for hit identification in recent years. The present work demonstrates the use of DEL technology identifying compound 16 as the first GFRa2/GFRa3 small molecule inhibitor (0.1/0.2 μM respectively) selective over RET. This molecule represents an opportunity to advance the development of small-molecule inhibitors targeting the GFRα-RET interface for the treatment of pain and itch.

2020-07-01·Cell Proliferation2区 · 生物学

The role of glial cell line‐derived neurotrophic factor family member artemin in neurological disorders and cancers

2区 · 生物学

ReviewOA

作者: Xu, Jiake ; Weng, Isabel Ziwai ; Zhu, Sipin ; Chen, Junhao ; Bennett, Samuel ; Xu, Huazi ; Li, Yihe ; Huang, Lin

AbstractArtemin (ARTN) is a member of the glial cell line‐derived neurotrophic factor (GDNF) family ligands (GFLs), which encompasses family members, GDNF, neurturin (NRTN) and persephin (PSPN). ARTN is also referred to as Enovin or Neublastin, and bears structural characteristics of the TGF‐β superfamily. ARTN contains a dibasic cleavage site (RXXR) that is predicted to be cleaved by furin to yield a carboxy‐terminal 113 amino acid mature form. ARTN binds preferentially to receptor GFRα3, coupled to a receptor tyrosine kinase RET, forming a signalling complex for the regulation of intracellular pathways that affect diverse outcomes of nervous system development and homoeostasis. Standard signalling cascades activated by GFLs via RET include the phosphorylation of mitogen‐activated protein kinase or MAPK (p‐ERK, p‐p38 and p‐JNK), PI3K‐AKT and Src. Neural cell adhesion molecule (NCAM) is an alternative signalling receptor for ARTN in the presence of GFRα1, leading to activation of Fyn and FAK. Further, ARTN also interacts with heparan sulphate proteoglycan syndecan‐3 and mediates non‐RET signalling via activation of Src kinases. This review discusses the role of ARTN in spinal cord injury, neuropathic pain and other neurological disorders. Additionally, ARTN plays a role in non‐neuron tissues, such as the formation of Peyer's patch‐like structures in the lymphoid tissue of the gut. The emerging role of ARTN in cancers and therapeutic resistance to cancers is also explored. Further research is necessary to determine the function of ARTN in a tissue‐specific manner, including its signalling mechanisms, in order to improve the therapeutic potential of ARTN in human diseases.

2019-11-01·The Laryngoscope1区 · 医学

Expression of trophic factors receptors during reinnervation after recurrent laryngeal nerve injury

1区 · 医学

Article

作者: Montalbano, Michael ; Tian, Likun ; Hernandez‐Morato, Ignacio ; Pitman, Michael J.

ObjectiveAn injury of the recurrent laryngeal nerve (RLN) triggers axonal regeneration but results in a poor functional recovery. Netrin‐1 and glial cell‐derived neurotrophic factor (GDNF) expression are up‐regulated in laryngeal muscles during RLN regeneration, but the role of their receptors produced in the nucleus ambiguus is unknown. The aim of this work was to determine the timing of the production of Netrin‐1 and GDNF receptors during RLN regeneration and correlate this with the previously identified timing of up‐regulation of their trophic factors in the laryngeal muscles.Study DesignLaboratory experiment with rat model.MethodsThe right RLN was transected and dextran amine tracer applied. At 7, 14, and 21 days postinjury (DPI), brainstems were removed and harvested. Immunostaining was performed for Netrin‐1 (deleted in colorectal carcinoma [DCC], UNC5A) and GDNF receptors (rearranged during transfection [Ret], glycosylphosphatidylinositol‐linked cell surface receptors [GFRα1, GFRα2, GFRα3]). The timing and type of receptor production relative to injury as well as their position in the nucleus ambiguus was analyzed.ResultsNetrin‐1 UNC5A receptors were minimal in the nucleus ambiguus during RLN regeneration. DCC, the receptor that plays an attract role, was immunopositive from 7 to 21 DPI. All GDNF receptors, except GFRα2, were clearly positive from 7 to 14 DPI. No differences of production were observed according to the position of the motor neurons in the nucleus ambiguus.ConclusionAn injury of the RLN leads to a higher production of Netrin‐1 DCC and GDNF receptors in the nucleus ambiguus. The timing of receptor production is similar to up‐regulation of their trophic factors in the laryngeal muscles.Level of EvidenceNA.Laryngoscope, 129:2537–2542, 2019