更新于：2024-09-19

PTPRM

更新于：2024-09-19

基本信息

别名

hR-PTPu、protein tyrosine phosphatase receptor type M、Protein-tyrosine phosphatase mu

+ [5]

简介

Receptor protein-tyrosine phosphatase that mediates homotypic cell-cell interactions and plays a role in adipogenic differentiation via modulation of p120 catenin/CTNND1 phosphorylation (PubMed:17761881, PubMed:10753936). Promotes CTNND1 dephosphorylation and prevents its cytoplasmic localization where it inhibits SLC2A4 membrane trafficking. In turn, SLC2A4 is directed to the plasma membrane and performs its glucose transporter function (PubMed:21998202).

关联

项与 PTPRM 相关的药物

RAD-601

靶点

PTPRM

作用机制

PTPRM抑制剂

在研机构-

原研机构

Case Western Reserve University School of Medicine

在研适应症-

非在研适应症

胶质母细胞瘤

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

RAD-602

靶点

PTPRM

作用机制

PTPRM抑制剂 [+1]

在研机构-

原研机构

Case Western Reserve University School of Medicine

在研适应症-

非在研适应症

胶质母细胞瘤

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

100 项与 PTPRM 相关的临床结果

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100 项与 PTPRM 相关的转化医学

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0 项与 PTPRM 相关的专利（医药）

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209

项与 PTPRM 相关的文献（医药）

2024-08-01·Kidney International

DNA methyltransferase 1 (DNMT1) promotes cyst growth and epigenetic age acceleration in autosomal dominant polycystic kidney disease

Article

作者: Zhou, Julie Xia ; Li, Xiaogang ; Calvet, James P ; Agborbesong, Ewud ; Harris, Peter C ; Li, Linda Xiaoyan ; Zhang, Hongbing

Alteration of DNA methylation leads to diverse diseases, and the dynamic changes of DNA methylation (DNAm) on sets of CpG dinucleotides in mammalian genomes are termed "DNAm age" and "epigenetic clocks" that can predict chronological age. However, whether and how dysregulation of DNA methylation promotes cyst progression and epigenetic age acceleration in autosomal dominant polycystic kidney disease (ADPKD) remains elusive. Here, we show that DNA methyltransferase 1 (DNMT1) is upregulated in cystic kidney epithelial cells and tissues and that knockout of Dnmt1 and targeting DNMT1 with hydralazine, a safe demethylating agent, delays cyst growth in Pkd1 mutant kidneys and extends life span of Pkd1 conditional knockout mice. With methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), DNMT1 chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis, we identified two novel DNMT1 targets, PTPRM and PTPN22 (members of the protein tyrosine phosphatase family). PTPRM and PTPN22 function as mediators of DNMT1 and the phosphorylation and activation of PKD-associated signaling pathways, including ERK, mTOR and STAT3. With whole-genome bisulfide sequencing in kidneys of patients with ADPKD versus normal individuals, we found that the methylation of epigenetic clock-associated genes was dysregulated, supporting that epigenetic age is accelerated in the kidneys of patients with ADPKD. Furthermore, five epigenetic clock-associated genes, including Hsd17b14, Itpkb, Mbnl1, Rassf5 and Plk2, were identified. Thus, the diverse biological roles of these five genes suggest that their methylation status may not only predict epigenetic age acceleration but also contribute to disease progression in ADPKD.

2024-02-13·Neurology

Genome-Wide Association Studies of 3 Distinct Recovery Phenotypes in Mild Ischemic Stroke

Article

作者: Hsu, Fang-Chi ; Cole, John W ; de Havenon, Adam ; Worrall, Bradford B ; Keene, Keith L ; Braun, Robynne ; Cramer, Steven C ; Aldridge, Chad M ; Lohse, Keith ; Lindgren, Arne G

BACKGROUND AND OBJECTIVESStroke genetic research has made substantial progress in the past decade. Its recovery application, however, remains behind, in part due to its reliance on the modified Rankin Scale (mRS) score as a measure of poststroke outcome. The mRS does not map well to biological processes because numerous psychosocial factors drive much of what the mRS captures. Second, the mRS contains multiple disparate biological events into a single measure further limiting its use for biological discovery. This led us to investigate the effect of distinct stroke recovery phenotypes on genetic variation associations with Genome-Wide Association Studies (GWASs) by repurposing the NIH Stroke Scale (NIHSS) and its subscores.METHODSIn the Vitamin Intervention for Stroke Prevention cohort, we estimated changes in cognition, motor, and global impairments over 2 years using specific measures. We included genotyped participants with a total NIHSS score greater than zero at randomization and excluded those with recurrent stroke during the trial. A GWAS linear mixed-effects model predicted score changes, with participant as a random effect, and included initial score, age, sex, treatment group, and the first 5 ancestry principal components.RESULTSIn total, 1,270 participants (64% male) were included with a median NIHSS score of 2 (interquartile range [IQR] 1-3) and median age 68 (IQR 59-75) years. At randomization, 20% had cognitive deficits (NIHSS Cog-4 score >0) and 70% had ≥1 motor deficits (impairment score >1). At 2 years, these percentages improved to 7.2% with cognitive deficits and 30% with motor deficits. GWAS identified novel suggestive gene-impairment associations (p < 5e^-6) for cognition (CAMK2D, EVX2, LINC0143, PTPRM, SGMS1, and SMAD2), motor (ACBD6, KDM4B, MARK4, PTPRS, ROBO1, and ROBO2), and global (MSR1 and ROBO2) impairments.DISCUSSIONDefining domain-specific stroke recovery phenotypes and using longitudinal clinical trial designs can help detect novel genes associated with chronic recovery. These data support the use of granular endpoints to identify genetic associations related to stroke recovery.

2023-11-01·Journal of Cellular and Molecular Medicine

A novel binding pocket in the D2 domain of protein tyrosine phosphatase mu (PTPmu) guides AI screen to identify small molecules that modulate tumour cell adhesion, growth and migration

Article

作者: Molyneaux, Kathleen ; Brady-Kalnay, Susann M ; Laggner, Christian

AbstractApproximately 40% of people will get cancer in their lifetime in the US, and 20% are predicted to die from the condition when it is invasive and metastatic. Targeted screening for drugs that interact with proteins that drive cancer cell growth and migration can lead to new therapies. We screened molecular libraries with the AtomNet® AI‐based drug design tool to identify compounds predicted to interact with the cytoplasmic domain of protein tyrosine phosphatase mu. Protein tyrosine phosphatase mu (PTPmu) is proteolytically downregulated in cancers such as glioblastoma generating fragments that stimulate cell survival and migration. Aberrant nuclear localization of PTPmu intracellular fragments drives cancer progression, so we targeted a predicted drug‐binding site between the two cytoplasmic phosphatase domains we termed a D2 binding pocket. The function of the D2 domain is controversial with various proposed regulatory functions, making the D2 domain an attractive target for the development of allosteric drugs. Seventy‐five of the best‐scoring and chemically diverse computational hits predicted to interact with the D2 binding pocket were screened for effects on tumour cell motility and growth in 3D culture as well as in a direct assay for PTPmu‐dependent adhesion. We identified two high‐priority hits that inhibited the migration and glioma cell sphere formation of multiple glioma tumour cell lines as well as aggregation. We also identified one activator of PTPmu‐dependent aggregation, which was able to stimulate cell migration. We propose that the PTPmu D2 binding pocket represents a novel regulatory site and that inhibitors targeting this region may have therapeutic potential for treating cancer.

项与 PTPRM 相关的新闻（医药）

2023-04-18

·GlobeNewswire-Health Care

Radiopharm Theranostics Enters Into Supply Agreement with TerThera for Terbium-161 Isotope

Agreement will supply Tb-161 for RAD 602, a potential first in class radiopharmaceutical for treatment of brain cancersSYDNEY, Australia, April 17, 2023 (GLOBE NEWSWIRE) -- Radiopharm Theranostics (ASX:RAD, “Radiopharm” or the “Company”), a developer of radiopharmaceutical products for both diagnostic and therapeutic uses, is pleased to announce an agreement with TerThera to supply the Company with Terbium-161 (Tb-161). The Tb-161 isotope will be linked to a proprietary peptide to form RAD 602, a radiotherapeutic that is being developed by Radiopharm to target protein tyrosine phosphatase mu (PTPmu or PTPμ). PTPμ is expressed in cancer cells but has limited expression in healthy tissue. Radiopharm will initiate a Phase I dose escalating trial of RAD 602 for treatment of patients with brain cancers during the fourth quarter of calendar 2023. “We are excited to initiate our RAD 602 clinical trial, which is the first dose escalating radiopharmaceutical study leveraging the strong therapeutic properties of Tb-161 in brain tumors,” said Riccardo Canevari, CEO and Managing Director of Radiopharm Theranostics. “This novel therapeutic isotope represents a potential first in class targeted radiotherapeutic that can expand treatment options for patients living with cancer. We believe that Radiopharm has achieved a strong competitive advantage from being the first company to do a phase I trial using this isotope, and securing supply of this relatively scarce isotope.” Terbium-161 is a highly promising isotope for targeted cancer treatment due to its unique characteristics of radiation emitted, which includes both Auger electrons and short-range beta particles. The beta radiation travels only a few millimeters and Auger electronic emission has a higher linear energy transfer that travels less than the width of a single cell. Tb‑161 has shown excellent bioequivalence presenting a biodistribution comparable to currently used radiolanthanides and is potentially superior to Lutetium-177 (Lu-177) due to Auger effect increasing potency and efficacy in selectively destroying tumor cells while leaving surrounding healthy tissue largely unaffected. “TerThera is positioned to meet the growing global demand for radioisotopes in oncology by providing a highly sustainable and uninterrupted supply of Terbium-161,” said Philippe van Overeem, CEO of TerThera. “We are proud to partner with Radiopharm Theranostics to supply their innovative radioligand pipeline and to help enable development of a new generation of therapeutic radiopharmaceuticals.” The costs associated with the purchase of Tb-161 are not material in relation to RAD’s annual budgeted expenditure and will be met from existing funds. The initial order for preclinical use is expected in April 2023, with the first order for clinical use expected in October 2023. The effective date of the supply agreement is 17 April 2023 and there are no material preconditions. The supply agreement is for an initial period of three years and may be extended for additional two years, unless agreed otherwise by either party. Cancellation provisions are at industry standard rates. Radiopharm will own all data generated and all inventions and discoveries made or conceived from its clinical trials. About TerThera BV TerThera is a radionuclide production focussed company based in The Netherlands. The founders and staff of TerThera have decades of experience in the nuclear medicine industry and are giving their full focus on the production of the innovative radionuclide Terbium-161 (Tb-161). TerThera is building a global platform to meet the growing demand for radionuclides in oncology and nuclear medicine. About Radiopharm Theranostics Radiopharm Theranostics is a clinical stage radiotherapeutics company developing a world-class platform of innovative radiopharmaceutical products for diagnostic and therapeutic applications in areas of high unmet medical need. Radiopharm has been listed on ASX (RAD) since November 2021. The company has a pipeline of six distinct and highly differentiated platform technologies spanning peptides, small molecules and monoclonal antibodies for use in cancer, in pre-clinical and clinical stages of development from some of the world’s leading universities and institutes. The pipeline has been built based on the potential to be first to market or best in class. The clinical program includes one Phase II and three Phase I trials in a variety of solid tumour cancers including breast, kidney and brain. Learn more at RadiopharmTheranostics.com. Authorised on behalf of the Radiopharm Theranostics board of directors by Executive Chairman Paul Hopper. For more information: Riccardo CanevariCEO & Managing DirectorP: +1 862 309 0293E: rc@radiopharmtheranostics.com Timothy McCarthyLifeSci Advisors, LLCP: +1 917 679 9282E: tim@lifesciadvisors.com Paul Hopper Executive Chairman P: +61 406 671 515 E: paulhopper@lifescienceportfolio.com MediaMatt WrightNWR CommunicationsP: +61 451 896 420E: matt@nwrcommunications.com.au Follow Radiopharm Theranostics: Website – https://radiopharmtheranostics.com/ Twitter – https://twitter.com/TeamRadiopharm Linked In – https://www.linkedin.com/company/radiopharm-theranostics/

引进/卖出放射疗法临床1期临床2期