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Last update 08 May 2025

NKX2-1

Last update 08 May 2025

Basic Info

Synonyms

BCH, Homeobox protein NK-2 homolog A, Homeobox protein Nkx-2.1

+ [10]

Introduction

Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differentiation phenotype. May play a role in lung development and surfactant homeostasis. Forms a regulatory loop with GRHL2 that coordinates lung epithelial cell morphogenesis and differentiation. Activates the transcription of GNRHR and plays a role in enhancing the circadian oscillation of its gene expression. Represses the transcription of the circadian transcriptional repressor NR1D1 (By similarity).

Drugs associated with NKX2-1

CircRMST

Target

NKX2-1 x SOX2

Mechanism

NKX2-1 inhibitors [+1]

Active Org.

Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences [+1]

Originator Org.

Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences [+1]

Active Indication

Neuroendocrine Tumors

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NKX2-1

100 Translational Medicine associated with NKX2-1

0 Patents (Medical) associated with NKX2-1

1,639

Literatures (Medical) associated with NKX2-1

01 Jun 2025·Journal of Hazardous Materials

Effects of early-life F-53B exposure on thyroid function in juvenile rats: The role of the cAMP signaling pathway

Article

Author: Zhang, Jing ; Li, Shen-Pan ; Zhao, Wen-Hui ; Bloom, Michael ; Jiang, Wen-Ting ; Dong, Guang-Hui ; Xiang, Ping ; Jalava, Pasi ; Zeng, Xiao-Wen ; Luo, Yi-Xin ; Zhu, Jia-Yi

Chlorinated polyfluoroalkyl ether sulfonate (F-53B), a substitute for perfluorooctane sulfonate (PFOS), exerts a stronger effect on neonatal thyroid hormone (TH) than PFOS. However, limited data on its thyrotoxicity complicates early-life risk assessment. Here, Sprague-Dawley rats were gavaged with F-53B (0, 8, 80, 800 μg/kg/d) for 63 days, from two weeks pre-pregnancy to two weeks post-weaning. The results showed F-53B accumulated in the juvenile rats thyroids, causing thyroid follicle colloid rupture and dysgenesis, marked by reduced thyroid transcription factor 1 and elevated paired box gene 8 expression. Furthermore, F-53B affects TH synthesis by decreasing the expression of thyroid peroxidase and thyroid-stimulating hormone receptor, and increasing type II deiodinase activity. In plasma, F-53B raised total thyroxine (TT4), suppressed free triiodothyronine and free thyroxine (FT4) levels, and lowered the FT4/TT4 ratio. Mechanistically, F-53B binds to the ligand-binding pockets of key downregulated genes (Calcitonin-related polypeptide alpha and Somatostatin) in the cyclic adenosine monophosphate (cAMP) pathway. This promoted the lower expressions of protein kinase A in the thyroid follicular cytoplasm and phosphorylated cAMP response element-binding protein (p-CREB1-S133) in the nucleus, potentially weakening TH synthesis genes transcription. Overall, this work provides pioneering insights into the thyrotoxicity mechanisms of F-53B, laying a foundation for endocrine risk assessment.

01 May 2025·Cancer Cytopathology

Clinicopathological and molecular characterization of non–small cell lung cancer with pericardial effusions

Article

Author: Seery, Peter P. ; Li, Tianhong ; Ma, Weijie ; Rodrigues Simoes, Nathalie J. ; Kerr, Darcy A. ; Tafe, Laura J. ; Liu, Xiaoying

AbstractBackgroundCytological evaluation is essential for assessing pericardial effusions (PEs) in non–small cell lung cancer (NSCLC). This study retrospectively examined the clinicopathological, molecular, and prognostic characteristics of patients with NSCLC with PE.MethodsClinical data from 80 patients with NSCLC with PE treated at an academic center over the course of 15 years were reviewed. PE specimens were categorized according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC). The analysis included patient demographics, molecular alterations, cytopathology, histology, and survival outcomes.ResultsOf the 80 patients, 36 (45%) were female and 90% had stage IV disease. A smoking history was noted in 58 patients (72.5%), and 22 patients (27.5%) presented with tamponade. Lung adenocarcinoma predominated (87.5%). The ISRSFC categorized 25% of the specimens as negative for malignancy (NFM), 7.5% as atypia of undetermined significance (AUS), 3.75% as suspicious for malignancy (SFM), and 63.75% as malignant (MAL). Immunohistochemistry in 57 specimens identified thyroid transcription factor 1 (65%) as the most frequently positive marker. Molecular analysis revealed p53 mutations (59.1%) as the most prevalent, followed by KRAS (34.1%) and EGFR (15.9%). Kaplan–Meier analysis showed significantly better survival for NFM patients than non‐NFM patients (MAL, SFM, and AUS; p = .0036). Bloody PEs and tamponade were associated with worse outcomes. The immunotherapy group achieved the most prolonged survival among stage IV patients (9.07 months; p = .017). Cox regression confirmed cytology‐negative status as an independent prognostic factor.ConclusionsCytological evaluation and ISRSFC classification are crucial for NSCLC‐associated PEs. A multidisciplinary approach integrating cytology, immunohistochemistry, and molecular profiling is essential for optimal management and prognosis.

01 Apr 2025·Thoracic Cancer

Metastasis of Small Cell Lung Cancer to the External Auditory Canal: A Case Report

Article

Author: Yoshida, Masamichi ; Goto, Hiroki ; Kodama, Shuuji ; Kobayashi, Tetsu ; Ito, Toshiyuki ; Fujiwara, Atsushi ; Miki, Hiroto ; Fujimoto, Hajime

ABSTRACTPatients with lung cancer often develop distant metastases; however, metastasis to the external auditory canal is rare. We report the case of a 77‐year‐old man who presented with left‐sided hearing loss, otalgia, and a red mass in the left external auditory canal. Computed tomography revealed masses in the left external auditory canal, lung, and pancreas. Histopathological analysis confirmed small cell lung cancer, with thyroid transcription factor 1 positivity in multiple lesions, suggesting a primary tumor in lung. Treatment with carboplatin and etoposide led to a reduction in metastatic lesions, including those in the external auditory canal, and improved hearing impairment. This case highlights a rare instance in which chemotherapy improved ear symptoms in a patient with small cell lung cancer metastasis to the external auditory. Written informed consent was obtained from the patient for the publication of this case report and accompanying images.

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NKX2-1

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