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Last update 08 May 2025

Noxa

Last update 08 May 2025

Basic Info

Synonyms

APR, Immediate-early-response protein APR, NOXA

+ [4]

Introduction

Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1 (By similarity). Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1.

Drugs associated with Noxa

Conjugate A1(Shenyang Pharmaceutical University)

Target

Bcl-2 x Noxa

Mechanism

Bcl-2 inhibitors [+1]

Active Org.

Shenyang Pharmaceutical University

Originator Org.

Shenyang Pharmaceutical University

Active Indication

Myeloid Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Noxa

100 Translational Medicine associated with Noxa

0 Patents (Medical) associated with Noxa

6,026

Literatures (Medical) associated with Noxa

01 Jul 2025·Biochemical Pharmacology

Oridonin combined with cisplatin synergistically induces apoptosis by activating the NOXA-BCL2 axis in esophageal squamous cell carcinoma

Article

Author: Liu, Bingrong ; Zhang, Jiyu ; Mao, Yue ; Guo, Qihang ; Zhou, Yangyang ; Zhao, Yue ; Li, Ying ; Yang, Huiyu ; Lv, Jinglong

Esophageal cancer, a malignant neoplasm originating from the epithelial cells of the esophagus, predominantly manifests as esophageal squamous cell carcinoma (ESCC) in approximately 90% of cases in China. Cisplatin-based chemotherapy regimens remain the first-line therapeutic option for ESCC, however, the five-year overall survival rate of patients is disappointingly low. Oridonin, a bioactive diterpenoid extracted from the traditional Chinese medicine herb Donglingcao, has demonstrated inhibitory effects against various malignancies. Currently, research on the combination of oridonin and cisplatin for the treatment of ESCC is limited. This study aims to elucidate the potential synergistic anti-cancer effects of oridonin in combination with cisplatin on ESCC, along with the underlying synergistic molecular mechanisms. In vitro experiments revealed that the combination of oridonin and cisplatin could synergistically inhibit ESCC cell proliferation, migration, invasion. The synergistic effect also induced cell cycle arrest and promoted apoptosis via the mitochondrial pathway by augmenting NOXA transcriptional activity and activating the NOXA-BCL2 axis. In vivo experiments corroborated these findings, showing a marked reduction in the growth of subcutaneous xenograft tumors in mice treated with the combination, without exacerbating the cisplatin-associated side effects such as weight loss or hepatic and renal toxicity. In conclusion, the combination of oridonin and cisplatin can synergistically inhibit the development of ESCC through the activation of the NOXA-BCL2 axis signaling pathway. This treatment is both safe and effective,presenting a promising prospect for combined therapeutic application in ESCC management.

01 Jun 2025·Immunology Letters

Neutrophil extracellular traps and reactive oxygen species: Predictors of prognosis in bladder cancer

Article

Author: Mansourabadi, Zahra ; Assarehzadegan, Mohammad-Ali ; Safari, Elahe ; Mehdipour, Fereshteh ; Faghih, Zahra ; Ariafar, Ali

Neutrophils, the most abundant leukocytes in circulation, have become the subject of intensive research due to growing evidence of their role as modulators of cancer with both anti- and pro-tumorigenic effects. However, their prognostic function related to the release of neutrophil extracellular traps (NETs) and production of reactive oxygen species (ROS) has not yet been elucidated in the context of bladder cancer (BC). This study aimed to evaluate the ability of circulating neutrophils from BC patients to undergo NETosis and produce ROS-both spontaneously and following activation with phorbol 12-myristate 13-acetate (PMA)-using flow cytometry and immunofluorescence techniques. Their relevance to clinicopathological characteristics was also evaluated. Our results showed that PMA-treated neutrophils had increased early NETosis in patients with stage II (P = 0.048) and T2 (P = 0.014) compared to those with stage III and T3, respectively. These cells also showed a significant increase in ROS production in patients with T2 compared to those with T3 (P = 0.026) and T4 (P = 0.014), as well as in patients with stage II compared to stage IV (P = 0.048). Additionally, spontaneous ROS production was higher in patients without lymphovascular invasion than in those with invasion (P = 0.013). The increased activity of neutrophils observed in earlier stages (stage II and T2) suggests a potential protective mechanism in the early phases of cancer progression. It also highlights NETosis and ROS production by neutrophils as possible biomarkers for assessing disease progression. These findings provide insights into the complex interactions of neutrophils within the tumor microenvironment and lay the groundwork for further investigations into targeted therapies, potentially improving prognostic evaluations and treatment outcomes for patients.

01 Jun 2025·Cytokine

Exosomes derived from myelodysplastic syndromes cells induce IL-1β production from macrophages to promote disease progress

Article

Author: Liu, Xiaoli ; Li, Peichun ; Deng, Ju ; Li, Shuo ; Ren, Fanggang ; Guan, Dongmei ; Wang, Hongwei ; Xu, Zhifang ; Zhang, HongYu ; Chen, Xiuhua

BACKGROUNDExosomes are extracellular vesicles with a membrane structure that play important roles in intercellular communication, material transport and cellular immunity.Our previous study found that exosomes can affect the biological functions of MDS cell lines, but the mechanism of action has not been elucidated.Macrophages are one of the major innate immune cells that produce a variety of inflammatory cytokines and perform multiple biological functions in the tumor microenvironment (TME).The role of tumor cell-derived exosomes on macrophages and in the progression of MDS is rarely reported,therefore, the aim of our study was to investigate the effect of exosomes on macrophages and the effect of cytokines secreted by macrophages on MDS cells, with a view to exploring the role and mechanisms of exosomes and macrophages in the progression of MDS.METHODSChanges in cytokine content in peripheral blood of MDS patients were detected. The cytokine concentration in the growth environment of MDS cell lines was changed to observe the changes in the biological functions of MDS cell lines.After induction of human monocyte cell line (THP-1) into THP-1-Mφ macrophages with Phorbol 12-myristate 13-acetate (PMA), the macrophages (Mφ) were then co-cultured with MDS cell line exosomes extracted by ultrafiltration with THP-1-Mφ to observe macrophage (Mφ) differentiation.Flow cytometry was used to detect the changes in cytokine content released by macrophages before and after the addition of exosome inhibitors, and the changes in the biological function of MDS cell lines during this process.Gene and protein levels of significantly changed cytokine-related signaling pathways were detected using Q-PCR and WB.RESULTSIL-1β levels were significantly higher in the peripheral blood of MDS patients compared to controls.The exosomes extracted by ultrafiltration can be taken up by macrophages, which can promote the release of IL-1β from THP-1-Mφ cells, and promote the proliferation, apoptosis and migration ability of MDS cell lines.Exosomes stimulate macrophages to produce IL-1β and promote MDS disease progression through the MER/ERK pathway.

News (Medical) associated with Noxa

04 Dec 2023

·www.prnewswire.com

Powered by Its Industry-Leading Comprehensive Multi-Omic Database, Caris Life Sciences to Showcase Research at the 2023 San Antonio Breast Cancer Symposium

In collaboration with leading cancer centers, research results to be presented from four studies across a breadth of breast tumor types and genomic alterations demonstrating Caris' impact on precision medicine IRVING, Texas, Dec. 4, 2023 /PRNewswire/ -- Caris Life Sciences®(Caris), the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI, today announced that the company and collaborators within the Caris Precision Oncology Alliance™ (POA) will collectively present findings at the San Antonio Breast Cancer Symposium (SABCS) that illustrate the potential impact of molecular profiling on the treatment of breast cancer. The findings demonstrate the power of Caris' comprehensive clinico-genomic database that enables novel insights into cancer that could have profound effects on a patient's diagnosis, prognosis, care plan, and response to treatment. SABCS is being held December 5-9, 2023 (Booth #1433) in San Antonio, Texas. Continue Reading "The San Antonio Breast Cancer Symposium continues to be the premiere conference for breast cancer research," said George W. Sledge, Jr., MD, Executive Vice President and Chief Medical Officer of Caris. "As part of our continuing commitment to the breast cancer community, Caris is proud to share important clinical/translational research created with our academic partners on important breast cancer questions." The research findings demonstrate the power of Caris' comprehensive clinico-genomic database Post this Presentations and posters from Caris include: Milan Radovich, PhD, Senior Vice President and Chief Scientific Officer of Caris, will participate in a Concurrent Educational Session entitled "Genomics for Clinical Research and Cancer Care" from 3:10 – 5:00 p.m. CT on Thursday, December 7 in the Stars at Night Ballroom 1-2. Dr. Radovich will deliver a presentation on "Emerging approaches to targeting pathways using precision medicine in breast cancer" from 3:10 – 3:40 p.m. before participating in a panel discussion from 4:40 – 5:00 p.m. "Precision oncology in breast cancer is rapidly evolving with the recent approval of several targeted therapies that rely on the detection of molecular biomarkers to inform selection. On the horizon are novel genomic and AI based approaches that will further shape the future treatment of this disease," said Dr. Radovich. "This education session at SABCS will highlight advances in new drug modalities and targetable pathways; liquid biopsies and clonal hematopoiesis; emerging evidence on treatment resistance; and the forefront of AI-enabled digital pathology for biomarker detection." A Caris study will be featured in the Concurrent Poster Spotlight Sessions Block 5 in the "PS13 Special Populations: Pregnancy, Male and Geriatric Patients" section on Thursday, December 7, from 5:30 – 6:30 p.m. CT in the Stars at Night Ballroom 3-4. The spotlight poster is titled "Molecular and Immunological Landscape of Sex-Based Differences in Breast Cancer: A Distinct Disease in Men" (Presentation #PS13-09). The study was performed in collaboration with Caris Precision Oncology Alliance™ (POA) members Dana-Farber Cancer Institute and Legorreta Cancer Center at Brown University, as well as others including the Mayo Clinic. In the featured study, the molecular and immunological landscapes of male and female breast cancer were investigated across 10,728 breast cancer samples (male, n=137; female, n=10,591) using Caris' Next-Generation Sequencing (NGS) technology. The results of this analysis indicate that male breast cancer has differential molecular and immune features compared to female breast cancer. A better understanding of these sex-based differences may help inform disease outcomes, provide a rationale for tailored therapeutic approaches, and guide the design of future treatments. "The Caris Precision Oncology Alliance™ continues its contribution to advancing breast cancer research by presenting novel findings on the molecular and immunological features of male breast cancer at this year's SABCS," said Chadi Nabhan, MD, MBA, FACP, Chairman of the POA. "By leveraging Caris' expansive real-world clinico-genomic database, our partner academic institutions are able to uncover new insights into the underpinnings of breast cancer biology leading to better therapeutic interventions." The POA includes 90 cancer centers, academic institutions, research consortia and healthcare systems, including 42 NCI-designated cancer centers, collaborating to advance precision oncology and biomarker-driven research. POA members work together to establish and optimize standards of care for molecular testing through innovative research focused on predictive and prognostic markers that improve the clinical outcomes for cancer patients. Additional Presentations Reveal Potential Impact of Comprehensive Molecular Profiling Caris will present additional data from studies demonstrating the critical role of precision medicine and molecular profiling in the treatment of breast cancer. All presentations will be made available online through Caris' website beginning December 7. Comprehensive Molecular and Immunological Characterization of Invasive Ductal Triple-Negative Breast Cancer (Presentation Number: PO4-24-01) This investigation of the molecular and immune signatures of invasive ductal (ID) triple-negative breast cancer (TNBC) aimed to improve understanding of TNBC biology to facilitate future identification of novel targets for treatment of this heterogenous disease. The results of this retrospective study of more than 13,000 breast cancer samples indicate that ID TNBC is associated with a distinct mutational and immunological profile compared to ID non-TNBC. ID TNBC is also associated with worse overall survival compared to ID non-TNBC. However, ID TNBC patients have improved survival post-pembrolizumab treatment. Comprehensive Characterization of BCL2 Family Genes in Metaplastic Triple Negative Breast Cancer (Presentation Number: PO4-24-02) This study aimed to investigate the expression of BCL2 family genes in metastatic TNBC. Results of this molecular profiling study suggest a strong association between higher expression of PMAIP1 and worse patient survival in this cancer. This association may potentially be attributable to higher immune checkpoint and stem cell-related gene expression, in addition to higher frequency of PD-L1 positivity in PMAIP1-High tumors. Further investigation is needed to prospectively validate PMAIP1 as a potential prognostic biomarker candidate in metaplastic TNBC. Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy (Presentation Number: PO4-24-08) Phyllodes tumors are rare tumors of the breast, a subset of which have considerable malignant potential. This study aimed to identify targetable alterations and enhance understanding of the mutational profiles of malignant phyllodes tumors (MPTs) to potentially enhance treatment options. NGS identified actionable genomic alterations, including an NTRK1 fusion and low HER2 transcriptional expression. These findings highlight the importance of NGS-based profiling, including RNA sequencing, in MPT research to uncover potential targeted treatment options for patients. About Caris Life Sciences Caris Life Sciences® (Caris) is the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms, Caris has created the large-scale, clinico-genomic database and computing capability needed to analyze and unravel the molecular complexity of disease. This convergence of sequencing power, big data and AI technologies provides an unmatched platform to deliver the next-generation of precision medicine tools for early detection, diagnosis, monitoring, therapy selection and drug development. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S., Europe, Asia and other international markets. To learn more, please visit CarisLifeSciences.com. Caris Life Sciences Media Contact: Lisa Burgner [email protected] 214.294.5606 SOURCE Caris Life Sciences

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Noxa

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