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Last update 08 May 2025

ITPRIPL1

Last update 08 May 2025

Basic Info

Synonyms

Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1, ITPRIP like 1, ITPRIPL1

+ [1]

Introduction

Functions as a ligand of CD3E, inhibiting TCR-CD3 complex signaling to regulate T cell activation. Induces stable CD3E-NCK1 binding, thereby preventing the CD3E-ZAP70 interaction and subsequently inhibiting the activation of the downstream ERK-NFkB signaling cascade and calcium influx.

Drugs associated with ITPRIPL1

BT02

Target

ITPRIPL1

Mechanism

ITPRIPL1 inhibitors

Active Org.

BioTroy Therapeutics

Originator Org.

BioTroy Therapeutics

Active Indication

Advanced Malignant Solid Neoplasm [+5]

Inactive Indication-

Drug Highest PhasePhase 1/2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ITPRIPL1

CTR20240083

/ RecruitingPhase 1/2

评估BT02在晚期实体瘤患者中的安全性、耐受性、药代动力学、免疫原性和初步抗肿瘤活性的开放标签I/II期研究

[Translation] An open-label Phase I/II study evaluating the safety, tolerability, pharmacokinetics, immunogenicity and preliminary anti-tumor activity of BT02 in patients with advanced solid tumors

评估BT02在晚期实体瘤患者中的安全性、耐受性、药代动力学、免疫原性和初步抗肿瘤活性的开放标签I/II期研究。

[Translation]

An open-label Phase I/II study evaluating the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of BT02 in patients with advanced solid tumors.

Start Date25 Jan 2024

Sponsor / Collaborator

BioTroy Therapeutics

NCT06404905

/ RecruitingPhase 1IIT

A First-in-Human, Open Label, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Antitumor Activity of BT02 in Patients With Advanced Solid Tumors

A First-in-Human, Open Label, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Antitumor Activity of BT02 in Patients with Advanced Solid Tumors

Start Date24 Jan 2024

Sponsor / Collaborator

Cancer Hospital Chinese Academy of Medical Sciences

ChiCTR2300075191

/ SuspendedEarly Phase 1IIT

A phase I open dose exploration study to evaluate the safety, tolerability, pharmacokinetic characteristics and anti-tumor efficacy of BT02 in patients with advanced solid tumors

Start Date01 Sep 2023

Sponsor / Collaborator

Shenzhen Sixth People's Hospital

100 Clinical Results associated with ITPRIPL1

100 Translational Medicine associated with ITPRIPL1

0 Patents (Medical) associated with ITPRIPL1

Literatures (Medical) associated with ITPRIPL1

01 Apr 2024·Cell

ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion

Article

Author: Quan, Yingfei ; Shen, Zan ; Xie, Lu ; Wang, Feng ; Ye, Rui ; Shi, Jiawei ; Sun, Yufan ; Wang, Shuhang ; Zhang, Yibo ; Brosseau, Jean-Philippe ; Shan, Lishen ; Fang, Yuan ; Deng, Shouyan ; Li, Ning ; Wang, Huanbin ; Chi, Hao ; Wang, Yonggang ; Liu, Grace ; Xu, Jie ; Wang, Yiting ; Liu, Jiayang ; Liang, Wenhua

Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical "signal one" phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.

10 Aug 2023·International journal of molecular sciences

Methylation Profile of Small Breast Cancer Tumors Evaluated by Modified MS-HRM.

Article

Author: Kometova, Vlada V ; Yarotskaya, Ekaterina L ; Krasnyi, Aleksey M ; Sukhikh, Gennadiy T ; Sadekova, Alsu A ; Rodionov, Valeriy V

The DNA methylation profile of breast cancer differs from that in healthy tissues and can be used as a diagnostic and prognostic biomarker. Aim of this study: To compare the levels of gene methylation in small malignant breast cancer tumors (<2 cm), in healthy tissue, and in fibroadenoma, and to evaluate the effectiveness of the modified Methylation Sensitive-High Resolution Melting (MS-HRM) method for this analysis. Analysis was performed using the modified MS-HRM method. For validation, the methylation levels of five genes were confirmed by pyrosequencing. The main study group included 96 breast cancer samples and the control group included 24 fibroadenoma samples and 24 healthy tissue samples obtained from patients with fibroadenoma. Breast cancer samples were divided into two subgroups (test set and validation set). The methylation of the following 15 genes was studied: MAST1, PRDM14, ZNF177, DNM2, SSH1, AP2M1, CACNA1E, CPEB4, DLGAP2, CCDC181, GCM2, ITPRIPL1, POM121L2, KCNQ1, and TIMP3. Significant differences in the validation set of samples were found for seven genes; the combination of the four genes GCM2, ITPRIPL1, CACNA1E, DLGAP2 (AUC = 0.99) showed the highest diagnostic value based on logistic regression for all breast cancer samples. Our modified MS-HRM method demonstrated that small breast cancer tumors have a specific DNA methylation profile that distinguishes them from healthy tissues and benign proliferative lesions.

01 Jan 2021·Technology in Cancer Research & TreatmentQ4 · MEDICINE

A Novel 10-Gene Signature Predicts Poor Prognosis in Low Grade Glioma

Q4 · MEDICINE

ArticleOA

Author: Zhang, Gentang ; Liu, Wentao ; Ren, Rijun ; Zou, Jiaxuan ; Liu, Jingping ; Wang, Maokai

Aim: Low grade glioma (LGG) is a lethal brain cancer with relatively poor prognosis in young adults. Thus, this study was performed to develop novel molecular biomarkers to effectively predict the prognosis of LGG patients and finally guide treatment decisions. Methods: survival-related genes were determined by Kaplan-Meier survival analysis and multivariate Cox regression analysis using the expression and clinical data of 506 LGG patients from The Cancer Genome Atlas (TCGA) database and independently validated in a Chinese Glioma Genome Atlas (CGGA) dataset. A prognostic risk score was established based on a linear combination of 10 gene expression levels using the regression coefficients of the multivariate Cox regression models. GSEA was performed to analyze the altered signaling pathways between the high and low risk groups stratified by median risk score. Results: We identified a total of 1489 genes significantly correlated with patients’ prognosis in LGG. The top 5 protective genes were DISP2, CKMT1B, AQP7, GPR162 and CHGB, the top 5 risk genes were SP1, EYA3, ZSCAN20, ITPRIPL1 and ZNF217 in LGG. The risk score was predictive of poor overall survival and relapse-free survival in LGG patients. Pathways of small cell lung cancer, pathways in cancer, chronic myeloid leukemia, colorectal cancer were the top 4 most enriched pathways in the high risk group. SP1, EYA3, ZSCAN20, ITPRIPL1, ZNF217 and GPR162 were significantly up-regulated, while DISP2, CKMT1B, AQP7 were down-regulated in 523 LGG tissues as compared to 1141 normal brain controls. Conclusions: The 10-gene signature may become novel prognostic and diagnostic biomarkers to considerably improve the prognostic prediction in LGG.

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ITPRIPL1

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