更新于：2024-11-01

多磷酸肌醇-5-磷酸酶

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与多磷酸肌醇-5-磷酸酶相关的药物

AQX-200 series (Neoleukin)

靶点

多磷酸肌醇-5-磷酸酶 x PI3K family

作用机制

多磷酸肌醇-5-磷酸酶刺激剂 [+1]

在研机构

Neoleukin Therapeutics, Inc.

原研机构

Neoleukin Therapeutics, Inc.

在研适应症

炎症

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

AQX-1000 series (Neoleukin)

靶点

多磷酸肌醇-5-磷酸酶 x PI3Kα

作用机制

多磷酸肌醇-5-磷酸酶刺激剂 [+1]

在研机构-

原研机构

Neoleukin Therapeutics, Inc.

在研适应症-

非在研适应症

血液肿瘤 [+1]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

LY-288975

靶点

多磷酸肌醇-5-磷酸酶

作用机制

多磷酸肌醇-5-磷酸酶抑制剂

在研机构-

原研机构

Lilly Research Center Ltd.

在研适应症-

非在研适应症

血液疾病 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与多磷酸肌醇-5-磷酸酶相关的临床结果

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100 项与多磷酸肌醇-5-磷酸酶相关的转化医学

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0 项与多磷酸肌醇-5-磷酸酶相关的专利（医药）

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248

项与多磷酸肌醇-5-磷酸酶相关的文献（医药）

2024-09-20·Plant biotechnology journal

KRN5b regulates maize kernel row number through mediating phosphoinositol signalling.

Article

作者: Shen, Xiaomeng ; Zhang, Zuxin ; Song, Weibin ; Zhao, Haiming ; Liu, Lei ; Li, Yunfu ; Zhao, Ran ; Qing, Xiangyu ; Jackson, David ; Tran, Thu ; Huang, Liangliang ; Lai, Jinsheng ; Li, Manfei ; Bai, Yan ; Ning, Qiang

Kernel row number (KRN) is a major yield related trait for maize (Zea mays L.) and is also a major goal of breeders, as it can increase the number of kernels per plant. Thus, identifying new genetic factors involving in KRN formation may accelerate improving yield-related traits genetically. We herein describe a new kernel number-related gene (KRN5b) identified from KRN QTL qKRN5b and encoding an inositol polyphosphate 5-phosphatase (5PTase). KRN5b has phosphatase activity towards PI(4,5)P₂, PI(3,4,5)P₃, and Ins(1,4,5)P₃ in vitro. Knocking out KRN5b caused accumulation of PI(4,5)P₂ and Ins(1,4,5)P₃, resulting in disordered kernel rows and a decrease in the number of kernels and tassel branches. The introgression of the allele with higher expression abundance into different inbred lines could increase the ear weight of the inbred lines and the corresponding hybrids by 10.1%-12.2% via increasing KRN, with no adverse effects on other agronomic traits. Further analyses showed that KRN5b regulates inflorescence development through affecting the synthesis and distribution of hormones. Together, KRN5b contributes to spikelet pair meristem development through inositol phosphate and phosphatidylinositols, making it a selecting target for yield improvement.

2024-09-01·Molecular Neurobiology

Inpp5e Regulated the Cilium-Related Genes Contributing to the Neural Tube Defects Under 5-Fluorouracil Exposure

Article

作者: Yue, Huixuan ; Zhu, Zhiqiang ; Wang, Jianhua ; Li, Shen ; Wang, Xiuwei ; Yang, Aiyun ; Guan, Zhen ; Yu, Jialu

Primary cilia are crucial for neurogenesis, and cilium-related genes are involved in the closure of neural tubes. Inositol polyphosphate-5-phosphatase (Inpp5e) was enriched in primary cilia and closely related to the occurrence of neural tube defects (NTDs). However, the role of Inpp5e in the development of NTDs is not well-known. To investigate whether Inpp5e gene is associated with the neural tube closure, we established a mouse model of NTDs by 5-fluorouracil (5-FU) exposure at gestational day 7.5 (GD7.5). The Inpp5e knockdown (Inpp5e^-/-) mouse embryonic stem cells (mESCs) were produced by CRISPR/Cas9 system. The expressions of Inpp5e and other cilium-related genes including intraflagellar transport 80 (Ift80), McKusick-Kaufman syndrome (Mkks), and Kirsten rat sarcoma viral oncogene homolog (Kras) were determined, utilizing quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, PCR array, and immunofluorescence staining. The result showed that the incidence of NTDs was 37.10% (23 NTDs/62 total embryos) and significantly higher than that in the control group (P < 0.001). The neuroepithelial cells of neural tubes were obviously disarranged in NTD embryos. The mRNA and protein levels of Inpp5e, Ift80, Mkks, and Kras were significantly decreased in NTD embryonic brain tissues, compared to the control (P < 0.05). Knockdown of the Inpp5e (Inpp5e^-/-) reduced the expressions of Ift80, Mkks, and Kras in mESCs. Furthermore, the levels of α-tubulin were significantly reduced in NTD embryonic neural tissue and Inpp5e^-/- mESCs. These results suggested that maternal 5-FU exposure inhibited the expression of Inpp5e, which resulted in the downregulation of cilium-related genes (Ift80, Mkks, and Kras), leading to the impairment of primary cilium development, and ultimately disrupted the neural tube closure.

2024-06-21·Human Molecular Genetics

Base editing correction of OCRL in Lowe syndrome: ABE-mediated functional rescue in patient-derived fibroblasts

Article

作者: Liu, Zhiquan ; Li, Tingting ; Lo, Chien-Hui ; Ning, Ke ; Sun, Yang ; Chen, Siyu ; Wang, Qing

AbstractLowe syndrome, a rare X-linked multisystem disorder presenting with major abnormalities in the eyes, kidneys, and central nervous system, is caused by mutations in OCRL gene (NG_008638.1). Encoding an inositol polyphosphate 5-phosphatase, OCRL catalyzes the hydrolysis of PI(4,5)P2 into PI4P. There are no effective targeted treatments for Lowe syndrome. Here, we demonstrate a novel gene therapy for Lowe syndrome in patient fibroblasts using an adenine base editor (ABE) that can efficiently correct pathogenic point mutations. We show that ABE8e-NG-based correction of a disease-causing mutation in a Lowe patient-derived fibroblast line containing R844X mutation in OCRL gene, restores OCRL expression at mRNA and protein levels. It also restores cellular abnormalities that are hallmarks of OCRL dysfunction, including defects in ciliogenesis, microtubule anchoring, α-actinin distribution, and F-actin network. The study indicates that ABE-mediated gene therapy is a feasible treatment for Lowe syndrome, laying the foundation for therapeutic application of ABE in the currently incurable disease.