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Last update 08 May 2025

NKX3-2

Last update 08 May 2025

Basic Info

Synonyms

Bagpipe homeobox protein homolog 1, BAPX1, Homeobox protein NK-3 homolog B

+ [5]

Introduction

Transcriptional repressor that acts as a negative regulator of chondrocyte maturation. PLays a role in distal stomach development; required for proper antral-pyloric morphogenesis and development of antral-type epithelium. In concert with GSC, defines the structural components of the middle ear; required for tympanic ring and gonium development and in the regulation of the width of the malleus (By similarity).

Drugs associated with NKX3-2

ICM-203

Target

NKX3-2

Mechanism

NKX3-2 modulators [+1]

Active Org.

ICM Biotech Australia Pty Ltd. [+2]

Originator Org.

ICM Co. Ltd.

Active Indication

Osteoarthritis, Knee [+2]

Inactive Indication-

Drug Highest PhasePhase 1/2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with NKX3-2

NCT05454566

/ Not yet recruitingPhase 1/2

A Single Dose Escalation Study of Intra-Articular ICM-203 in Subjects With Kellgren-Lawrence Grade 2 or Grade 3 Osteoarthritis of the Knee

The purpose of this study is to determine the safety, tolerability, and activity of ICM-203, a recombinant adeno-associated viral (AAV) vector that expresses a therapeutic gene that promotes cartilage formation, reduces joint inflammation and pain, as well as improves joint physical function, by injecting escalating doses of ICM-203 into the knee of subjects with mild to moderate knee osteoarthritis (OA).
Approximately 6 to 18 subjects will be enrolled into 3 successive dose-escalating groups in a 3+3 study design, whereby 3 study subjects in each group will be dosed sequentially with ICM-203 and 3 additional subjects will be dosed at the same dose level if a dose limiting toxicity (DLT) occurs in any of the first 3 subjects.

Start Date15 Nov 2025

Sponsor / Collaborator

ICM Co. Ltd.

NCT05752032

/ Enrolling by invitationNot Applicable

A Long Term Follow-up Study of Subjects Who Received ICM-203 or Matching Placebo

This is an observational study of the long term safety and efficacy of ICM-203.

Start Date16 Mar 2023

Sponsor / Collaborator

ICM Co. Ltd.

NCT04875754

/ Active, not recruitingPhase 1/2

A Phase 1/2a, Double-Blind, Placebo-Controlled Single Dose Escalation Study of Intra-Articular ICM 203 in Subjects With Kellgren-Lawrence Grade 2 or Grade 3 Osteoarthritis of the Knee

Start Date17 Mar 2022

Sponsor / Collaborator

ICM Biotech Australia Pty Ltd.

100 Clinical Results associated with NKX3-2

100 Translational Medicine associated with NKX3-2

0 Patents (Medical) associated with NKX3-2

143

Literatures (Medical) associated with NKX3-2

01 Mar 2025·The Innovation

Multi-level genomic convergence of secondary aquatic adaptation in marine mammals

Article

Author: Shan, Lei ; Xu, Zhikang ; Liang, Na ; Zhang, Zhenhua ; Chai, Simin ; Sun, Linxia ; Chen, Yongjie ; Yu, Zhenpeng ; Ren, Wenhua ; Sun, Di ; Tian, Ran ; Zhou, Ming ; Zhang, Qian ; Zheng, Yu ; Seim, Inge ; Yang, Guang ; Deme, Luoying ; Yin, Daiqing ; Wu, Tianzhen ; Xu, Shixia

Marine mammals provide a valuable model for studying the molecular basis of convergent evolution during secondary aquatic adaptation. Using multi-omics data and functional experiments, including CRISPR-Cas9 mouse models and luciferase reporter assays, this study explored the molecular mechanisms driving this transition across coding regions, regulatory elements, and genomic architecture. Convergent amino acid substitutions in APPL1 ^P378L and NEIL1 ^E71G were found to promote lipid accumulation and suppress cancer cell proliferation, likely contributing to the evolution of extensive blubber layers and cancer resistance. Convergently evolved conserved non-exonic elements (CNEs) and lineage-specific regulatory variations were shown to influence the activity of nearby genes (e.g., NKX3-2, SOX9, HAND2), shaping cetacean limb phenotypes. Additionally, convergent shifts in topologically associating domains (TADs) across cetaceans and pinnipeds were implicated in the regulation of ASXL3 and FAM43B expression, playing a role in the formation of thickened blubber layers and mitigating cancer susceptibility. Structural variations within conserved TADs were associated with the expression of neuronal genes, including NUP153 and ID4, potentially driving cognitive and social adaptations. These findings provide novel insights into the molecular foundations of the convergent evolution of secondary aquatic adaptations in mammals.

01 Jan 2025·Heliyon

Development and validation of a biomarker-based prediction model for metastasis in patients with colorectal cancer: Application of machine learning algorithms

Article

Author: Afshar, Saeid ; Farashi, Sajjad ; Tapak, Leili ; Ayubi, Erfan

ObjectiveThe purpose of the current study was to develop and validate a biomarker-based prediction model for metastasis in patients with colorectal cancer (CRC).MethodsTwo datasets, GSE68468 and GSE41568, were retrieved from the Gene Expression Omnibus (GEO) database. In the GSE68468 dataset, key biomarkers were identified through a screening process involving differential expression analysis, redundancy analysis, and recursive feature elimination technique. Subsequently, the prediction model was developed and internally validated using five machine learning (ML) algorithms including lasso and elastic-net regularized generalized linear model (glmnet), k-nearest neighbors (kNN), support vector machine (SVM) with Radial Basis Function Kernel, random forest (RF), and eXtreme Gradient Boosting (XGBoost). The predictive performance of the algorithm with the highest accuracy was then externally validated on the GSE41568 dataset.ResultsAmong 22,283 registered genes in the GSE68468 dataset, the screening process identified 16 key genes including MMP3, CCDC102B, CDH2, SCGB1A1, KRT7, CYP1B1, LAMC3, ALB, DIXDC1, VWF, MMP1, CYP4B1, NKX3-2, TMEM158, GADD45B, SERPINA1 and these genes were used to build the prediction model. On the internal validation dataset, the prediction performance of five ML algorithms was as follows; RF (accuracy = 0.97 and kappa = 0.91), XGBoost (0.93, 0.81), kNN (0.93, 0.81), glmnet (0.93, 0.82) and SVM (0.92, 0.80). Top five biomarkers were MMP3, CCDC102B, CDH2, VWF and MMP1. The RF model exhibited an accuracy of 0.97, a kappa value of 0.92, and an area under the curve (AUC) of 0.99 in the external validation dataset.ConclusionThe results of this study have identified biomarkers through ML algorithms which help to identify patients with CRC prone to metastasis.

01 Nov 2024·Science Advances

Suppression of non-muscle myosin II boosts T cell cytotoxicity against tumors

Article

Author: Lin, Feng ; Xiong, Chunyang ; Cao, Xinyuan ; Pang, Ruiyang ; Li, Kailong ; Liao, Wanying ; Kong, Jie ; Liu, Yuying ; Wang, Dingding ; Yu, Donglin ; Zhang, Ning ; Yu, Tao ; Sun, Weihao ; Yang, Yingyun ; Yang, Qianyi ; Song, Xiaowei ; Zhang, Ziyi ; Wen, Dahan ; Zhang, Lei ; Liang, Junbo

Increasing evidence highlights the importance of immune mechanoregulation in establishing and sustaining tumor-specific cytotoxicity required for desirable immunotherapeutic outcomes. However, the molecular connections between mechanobiological inputs and outputs and the designated immune activities remain largely unclear. Here, we show that partial inhibition of non-muscle myosin II (NM II) augmented the traction force exerted by T cells and potentiated T cell cytotoxicity against tumors. By using T cells from mice and patients with cancer, we found that NM II is required for the activity of NKX3-2 in maintaining the expression of ADGRB3, which shapes the filamentous actin (F-actin) organization and ultimately attributes to the reduced traction force of T cells in the tumor microenvironment. In animal models, suppressing the NM II–NKX3-2–ADGRB3 pathway in T cells effectively suppressed tumor growth and improved the efficacy of the checkpoint-specific immunotherapy. Overall, this work provides insights into the biomechanical regulation of T cell cytotoxicity that can be exploited to optimize clinical immunotherapies.

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NKX3-2

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