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Last update 08 May 2025

GNAI2

Last update 08 May 2025

Basic Info

Synonyms

Adenylate cyclase-inhibiting G alpha protein, G protein subunit alpha i2, GIP

+ [3]

Introduction

Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool. Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division.

Drugs associated with GNAI2

US20220340526

Patent Mining

Target

EGF x GNAI2

Mechanism

GNAI2 inhibitors

Active Org.

The Georgia Tech Research Corp.

Originator Org.

The Georgia Tech Research Corp.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GNAI2

100 Translational Medicine associated with GNAI2

0 Patents (Medical) associated with GNAI2

169

Literatures (Medical) associated with GNAI2

27 Mar 2025·Combinatorial Chemistry & High Throughput Screening

Exploring Mechanisms of Ephx2 in Treating Atherosclerosis Using Independent Cascade Model and Adverse Outcome Pathways

Article

Author: An, Jinbing ; Dai, Yuanwen ; Chen, Yong ; Pang, Wei ; Cao, Bo ; Zhang, Caiyuzhen

Background:Atherosclerosis (AS) is a leading cause of cardiovascular diseases, characterized by lipid accumulation in arterial walls. The enzyme Ephx2 (soluble epoxide hydrolase, sEH) is implicated in AS development, but its precise mechanisms and therapeutic potential are not fully understood.Objectives:This study aimed to analyze gene expression data from low-density lipoprotein receptor knockout (LDLR⁸/⁸) and LDLR⁸/⁸sEH⁸/⁸ mice to identify significant genes associated with AS.Methods:A directed compound-protein interaction network was constructed based on these genes and related pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the end, through resistance distance (RD) between any two nodes in this network, the Independent Cascade (IC) model was applied to explore Ephx2 mechanisms in AS, such as important Adverse Outcome Pathways (AOPs).Results:Several AOPs were identified as critical in AS treatment via Ephx2. The key AOPs included inflammatory response and cytokine release, cholesterol deposition and oxidation, disruption of plaque stability, smooth muscle cell proliferation and migration, and platelet activation and coagulation. Within the top AOPs of inflammatory response and cytokine release, potential target genes were identified, such as Mapk3, PiK3cd, Gnai2, Mapk10, Arnt, and RhoA. Critical paths from Ephx2 to these target genes were established, suggesting mechanisms by which Ephx2 may influence AS pathogenesis.Conclusion:By defining the AS network and corresponding RD, this study elucidated potential mechanisms by which Ephx2 affects AS through specific KEGG pathways, AOPs, and target genes. These findings enhanced the understanding of AS pathogenesis and highlighted potential targets like Mapk3 for developing therapeutic strategies in AS prevention and treatment.

24 Jan 2025·Nucleic Acids Research

RNA G-quadruplex structure-based PROTACs for targeted DHX36 protein degradation and gene activity modulation in mammalian cells

Article

Author: Dai, Tianle ; Wang, Huating ; Chen, Xiaona ; Zhang, Kun ; Li, Maolin ; Kwok, Chun Kit ; Zhao, Haizhou ; Chen, Shuo-Bin ; Zhong, Liting ; Guo, Xiaofan ; Nie, Qichang ; Lau, Terrence Chi-Kong

AbstractRNA G-quadruplexes (rG4s) are non-canonical secondary nucleic acid structures found in the transcriptome. They play crucial roles in gene regulation by interacting with G4-binding proteins (G4BPs) in cells. rG4-G4BP complexes have been associated with human diseases, making them important targets for drug development. Generating innovative tools to disrupt rG4-G4BP interactions will provide a unique opportunity to explore new biological mechanisms and potentially treat related diseases. Here, we have rationally designed and developed a series of rG4-based proteolytic targeting chimeras (rG4-PROTACs) aimed at degrading G4BPs, such as DHX36, a specific G4BP that regulates gene expression by binding to and unraveling rG4 structures in messenger RNAs (mRNAs). Our comprehensive data and systematic analysis reveals that rG4-PROTACs predominantly and selectively degrade DHX36 through a proteosome-dependent mechanism, which promotes the formation of the rG4 structure in mRNA, leading to the translation inhibition of rG4-containing transcripts. Notably, rG4-PROTACs inhibit rG4-mediated APP protein expression, and impact the proliferative capacity of skeletal muscle stem cells by negatively regulating Gnai2 protein expression. In summary, rG4-PROTACs provide a new avenue to understand rG4-G4BP interactions and the biological implications of dysregulated G4BPs, promoting the development of PROTACs technology based on the non-canonical structure of nucleic acids.

01 Dec 2024·Neurological Sciences

A new variant confirms GNAI2 as a rare cause of periventricular nodular heterotopia

Article

Author: Decio, Alice ; Bassi, Maria Teresa ; D'Angelo, Maria Grazia ; Panzeri, Elena ; Agarwal, Nivedita

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