Request Demo

Last update 08 May 2025

PTPRM

Last update 08 May 2025

Basic Info

Synonyms

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

+ [5]

Introduction

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:10753936, PubMed:17761881). 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).

Drugs associated with PTPRM

RAD-602

Target

PTPRM

Mechanism

PTPRM inhibitors [+1]

Active Org.-

Originator Org.

Case Western Reserve University School of Medicine

Active Indication-

Inactive Indication

Glioblastoma

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

RAD-601

Target

PTPRM

Mechanism

PTPRM inhibitors

Active Org.-

Originator Org.

Case Western Reserve University School of Medicine

Active Indication-

Inactive Indication

Glioblastoma

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PTPRM

100 Translational Medicine associated with PTPRM

0 Patents (Medical) associated with PTPRM

Literatures (Medical) associated with PTPRM

01 Mar 2025·Journal for ImmunoTherapy of Cancer

New soluble CSF-1R-dimeric mutein with enhanced trapping of both CSF-1 and IL-34 reduces suppressive tumor-associated macrophages in pleural mesothelioma

Article

Author: Anegon, Ignacio ; LeBihan, Héloïse ; Remy, Séverine ; Salama, Apolline ; Deshayes, Sophie ; Maillasson, Mike ; Guillonneau, Carole ; Humeau, Romain ; Blanquart, Christophe ; Mortier, Erwan ; Fresquet, Judith ; Quéméner, Agnès ; Joalland, Noémie

BackgroundColony stimulating factor-1 receptor (CSF-1R) and its ligands CSF-1 and interleukin (IL)-34 have tumorigenic effects through both induction of suppressive macrophages, and survival/proliferation of tumor cells. In addition, the IL-34 tumorigenic effect can also be mediated by its other receptors, protein-tyrosine phosphatase zeta, Syndecan-1 (CD138) and triggering receptor expressed on myeloid cells 2. Small tyrosine kinase inhibitors are used to block CSF-1R signaling but lack specificity. Neutralizing anti-CSF-1 and/or IL-34 antibodies have been proposed, but their effects are limited. Thus, there is a need for a more specific and yet integrative approach.MethodsA human mutated form of the extracellular portion of CSF-1R was in silico modelized to trap both IL-34 and CSF-1 with higher affinity than the wild-type CSF-1R by replacing the methionine residue at position 149 with a Lysine (M149K). The extracellular portion of the mutated CSF-1RM149Kwas dimerized using the immunoglobulin Fc sequence of a silenced human IgG1 (sCSF-1RM149K-Fc). Signaling through CSF-1R, survival of monocytes and differentiation of suppressive macrophages were analyzed using pleural mesothelioma patient's samples and mesothelioma/macrophage spheroids in vitro and in vivo in the presence of sCSF-1RM149K-Fc or sCSF-1R-Fc wild type control (sCSF-1RWT-Fc).ResultsWe defined that the D1 to D5 domains of the extracellular portion of CSF-1R were required for efficient binding to IL-34 and CSF-1. The mutein sCSF-1RM149K-Fc trapped with higher affinity than sCSF-1RWT-Fc both CSF-1 and IL-34 added in culture and naturally produced in mesothelioma pleural effusions. sCSF-1RM149K-Fc inhibited CSF-1R signaling, survival and differentiation of human suppressive macrophage in vitro and in vivo induced by pleural mesothelioma cells. Neutralization of IL-34 and CSF-1 by sCSF-1RM149K-Fc also resulted in higher killing of pleural mesothelioma cells by a tumor-specific CD8+T cell clone in mesothelioma/macrophage spheroids.ConclusionssCSF-1RM149K-Fc efficiently traps both CSF-1 and IL-34 and inhibits CSF-1R signaling, monocyte survival and suppressive macrophage differentiation induced by pleural mesothelioma cells producing CSF-1 and IL-34, as well as restores cytotoxic T-cell responses. sCSF-1RM149K-Fc has therapeutic potential vs other therapies under development targeting single components of this complex cytokine pathway involved in cancer.

01 Nov 2024·Psychiatry and Clinical Neurosciences

Identification of risk loci for postpartum depression in a genome‐wide association study

Article

Author: Li, Xue ; Kikuchi, Saya ; Hoshiai, Tetsuro ; Ozaki, Norio ; Kuriyama, Shinichi ; Tomita, Hiroaki ; Matsuki, Tasuku ; Warita, Noriko ; Shoji, Tomoka ; Ogishima, Soichi ; Ono, Chiaki ; Metoki, Hirohito ; Sakurai‐Yageta, Mika ; Nakamura, Tomohiro ; Takahashi, Ippei ; Ishikuro, Mami ; Saito, Masatoshi ; Nakamura, Yukako ; Fuse, Nobuo ; Yaegashi, Nobuo ; Sugawara, Junichi ; Murakami, Keiko ; Nagami, Fuji ; Tamiya, Gen ; Ohseto, Hisashi ; Kobayashi, Natsuko ; Narita, Akira ; Ueno, Fumihiko ; Yu, Zhiqian ; Takahashi, Nagahide ; Yamamoto, Masayuki ; Kikuya, Masahiro ; Obara, Taku ; Kinoshita, Kengo

AimGenome‐wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD‐associated loci.MethodsThe first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders.ResultsA meta‐analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10−8) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over‐represented in categories including long‐term depression, GnRH signaling, glutamatergic synapse, oxytocin signaling, and Rap1 signaling.ConclusionThe current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis.

01 Aug 2024·Kidney International

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

Article

Author: Zhou, Julie Xia ; Calvet, James P ; Li, Xiaogang ; 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.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

PTPRM

Basic Info

Related

Analysis