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Last update 08 May 2025

ITPR

Last update 08 May 2025

Basic Info

Synonyms

Inositol triphosphate receptors, InsP3R

Introduction-

Drugs associated with ITPR

INNOVA-102

Target

ITPR3

Mechanism

ITPR3 antagonists

Active Org.-

Originator Org.

Innovatis Pharma Corp

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ITPR

100 Translational Medicine associated with ITPR

0 Patents (Medical) associated with ITPR

6,882

Literatures (Medical) associated with ITPR

01 Jun 2025·American Journal of Ophthalmology

Genetic Distinctions Between Reticular Pseudodrusen and Drusen: A Genome-Wide Association Study

Article

Author: Khalid, Hagar ; Egan, Catherine ; Phatak, Sumita ; Valmaggia, Philippe ; Khawaja, Anthony P ; de Vente, Coen ; Liakopoulos, Sandra ; Sánchez, Clara I ; Schwartz, Roy ; Olvera-Barrios, Abraham ; Tufail, Adnan ; Luben, Robert ; Bonelli, Roberto ; Warwick, Alasdair N ; Jhingan, Mahima

OBJECTIVETo identify genetic determinants specific to reticular pseudodrusen (RPD) compared with drusen.DESIGNGenome-wide association study (GWAS) SUBJECTS: Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort.METHODSParticipants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort, were included. A deep learning framework analyzed 169,370 optical coherence tomography (OCT) volumes to identify cases and controls within the UKBB. Five retina specialists validated the cohorts using OCT and color fundus photographs. Several GWAS were undertaken utilizing the quantity and presence of RPD and drusen. Genome-wide significance was defined as P < 5e-8.MAIN OUTCOMES MEASURESGenetic associations were examined with the number of RPD and drusen within 'pure' cases, where only RPD or drusen were present in either eye. A candidate approach assessed 46 previously known AMD loci. Secondary GWAS were conducted for number of RPD and drusen in mixed cases, and binary case-control analyses for pure RPD and pure drusen.RESULTSThe study included 1787 participants: 1037 controls, 361 pure drusen, 66 pure RPD, and 323 mixed cases. The primary pure RPD GWAS identified four genome-wide significant loci: rs11200630 near ARMS2-HTRA1 (P = 1.9e-09), rs79641866 at PARD3B (P = 1.3e-08), rs143184903 near ITPR1 (P = 8.1e-09), and rs76377757 near SLN (P = 4.3e-08). The latter three are uncommon variants (minor allele frequency <5%). A significant association at the CFH locus was also observed using a candidate approach (P = 1.8e-04). For pure drusen, two loci reached genome-wide significance: rs10801555 at CFH (P = 6.0e-33) and rs61871744 at ARMS2-HTRA1 (P = 4.2e-20).CONCLUSIONSThe study highlights a clear association between the ARMS2-HTRA1 locus and higher RPD load. Although the CFH locus association did not achieve genome-wide significance, a suggestive link was observed. Three novel associations unique to RPD were identified, albeit for uncommon genetic variants. Further studies with larger sample sizes are needed to explore these findings.

01 Jun 2025·Biochemical and Biophysical Research Communications

Role of IP3R2-Mediated mitochondrial calcium homeostasis in early hypoxic stress injury of retinal pigment epithelial cells

Article

Author: Zhu, Hong ; Wang, Yuchen ; Jiang, Jingjing ; Wei, Fang ; Xu, Li

OBJECTIVETo investigate the regulatory role of IP3R2 on mitochondrial function in retinal pigment epithelial cells during the early stage of hypoxic stress preceding apoptosis.METHODSARPE-19 cell line was cultured in 1 % oxygen to establish an in vitro hypoxic model. The presence of hypoxia and absence of significant apoptosis in RPE cells were confirmed through hypoxia-inducible factor HIF-1α expression and apoptosis assays respectively. Mitochondrial function was evaluated using an ATP assay kit and flow cytometry. Immunoblotting was conducted to ascertain the expression levels of mitochondrial dynamics proteins (MFN2, DRP1, TOMM20) and mitochondrial calcium-related proteins (IP3R1, IP3R2, IP3R3, VDAC1). Mitochondrial morphology was observed using confocal microscopy. The impact of small interfering RNA (siRNA)-mediated IP3R2 knockdown on apoptosis and mitochondrial function was assessed in RPE cells.RESULTSUnder hypoxic stress before the onset of apoptosis in RPE cells, mitochondrial dysfunction and significant increase in mitochondrial calcium flux were observed, accompanied by a notable upregulation of IP3R2 expression under hypoxia. Knockdown of IP3R2 during the pre-apoptotic stage further impaired RPE function under hypoxia.CONCLUSIONIP3R2-mediated mitochondrial calcium overload is crucial for maintaining RPE function and mitochondrial homeostasis during the pre-apoptotic stage triggered by hypoxic stress.

01 Jun 2025·Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology

Insight into Ca2+- inositol 1,4,5-trisphosphate receptor 2 (IP3R2)-mediated unfolded protein response and apoptosis in scallop Patinopecten yessoensis under high temperature stress

Article

Author: Wang, Lingling ; Yang, Chuanyan ; Song, Linsheng ; Jiang, Dongli ; Ma, Xiaoxue ; Fan, Hongmei ; Gu, Wenfei

Inositol 1,4,5-trisphosphate receptor 2 (IP₃R2) is an essential Ca²⁺ release channel protein located in the endoplasmic reticulum (ER), and plays a significant role in responding to various environmental stimuli. In the present study, the function of IP₃R2 from Yesso scallop Patinopecten yessoensis (PyIP₃R2) in regulating the Ca²⁺-mediated unfolded protein response (UPR) and apoptosis after high temperature (25 °C) treatment was investigated. Three MIR domains, one RYDR_ITPR domain, one RIH_assoc domain and one Ion_trans domain were identified in PyIP₃R2. Both D-myo-inositol-1,4,5-triphosphate (IP3, an activator of IP₃R) and high temperature significantly upregulated the mRNA expression level of PyIP₃R2 and genes related to apoptosis and the UPR, and also increased intracellular Ca²⁺ content (p < 0.05). Furthermore, the IP₃R antagonist 2-aminoethyl diphenylborinate (2-APB) had the opposite effect, decreasing intracellular Ca²⁺ content and the mRNA expression level of PyIP₃R2, glucose regulated protein 78 (PyGRP78) and PyCaspase-3 (p < 0.05). However, the apoptosis rate and Caspase-3 activity remained comparable to those in the injection control group. These findings indicate that PyIP₃R2 mediates UPR and apoptosis in scallop haemocytes by regulating Ca²⁺content and distribution, and providing insight into the cellular responses of scallops to high temperature.

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