This phase Ib/II trial tests the safety, side effects, best dose and how well giving CX-5461 works for the treatment of patients with B-cell non-Hodgkin lymphoma. CX-5461 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CX-5461 may be safe, tolerable and/or effective in treating patients with B-cell non-Hodgkin lymphoma.

Start Date19 Sep 2025

Sponsor / Collaborator

National Cancer Institute

NCT06606990

/ RecruitingPhase 1IIT

Pilot Study of Pidnarulex Pharmacodynamics in Patients With Advanced Solid Tumors

This phase I trial tests the safety, side effects, and best dose of pidnarulex (CX-5461) in treating patients with solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic). Pidnarulex is an oral inhibitor of ribonucleic acid polymerase I, with potential antineoplastic activity. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill cancer cells.

Start Date01 Jul 2025

Sponsor / Collaborator

National Cancer Institute

NCT05425862

/ SuspendedPhase 1IIT

Phase 1 Trial of Pidnarulex and Talazoparib in Patients With Metastatic Castration Resistant Prostate Cancer

This is phase I, open label, multicentre, dose-escalation study where both doses of talazoparib and pidnarulex will be escalated to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the combination. It is possible that either 1 or 2 RP2D of the combination will be defined at the end of the study. Patients with disease that is deemed to be amendable to repeated tumour biopsies will be invited to undergo optional paired biopsies: at baseline and Cycle 1 Day 9 + 3 days and at the time of progression. Pidnarulex will be given as an IV infusion on days 1 and 8 of a 28 day cycle and talazoparib will be taken once daily continuously. Disease status will be assessed at regular intervals by CT scans, radionuclide bone scans, and PSA. Throughout the study, safety and tolerability will be assessed and established procedures for management of toxicities will be applied

Start Date21 Oct 2022

Sponsor / Collaborator

Peter MacCallum Cancer Institute

100 Clinical Results associated with Pidnarulex

100 Translational Medicine associated with Pidnarulex

100 Patents (Medical) associated with Pidnarulex

209

Literatures (Medical) associated with Pidnarulex

01 Nov 2025·CELLULAR SIGNALLING

CX-5461 inhibits cell proliferation and induces ferroptosis of colorectal cancer cells by inactivating Nrf2 pathway

Article

Author: Zhang, Ruixue ; Piao, Junjie ; Cong, Xinyu ; Jin, Aihua ; Yang, Wenqing ; Zhang, Yu ; Xiao, Wenjing ; Chang, Xiaolu ; Wang, Qingkun ; Lin, Zhenhua

Ferroptosis is a newly identified type of cell death, characterized by iron dependent lipid peroxidation. Triggering ferroptosis is considered a promising target, and efforts have been made to identify ferroptosis inducers in cancer. CX-5461 is a RNA polymerase I inhibitors that has been approved by FDA to treat breast and ovarian cancer patients with BRCA1/2 mutations. In our previous study, we found that CX-5461 inhibited GSH synthesis and promote lipid peroxidation in colorectal cancer (CRC) cells, suggesting that CX-5461 could induce ferroptosis. Therefore, we aim to elucidate the anti-cancer activity of CX-5461 in CRC,and the mechanisms of CX-5461-mediated ferroptosis. As a result, we found that CX-5461 inhibited the proliferation of CRC cells, determined by CCK-8, EdU and colony formation assay. RNA-seq analysis suggested that differentially expressed genes (DEGs) were related to cell adhesion molecular, focal adhesion, and cell cycle, etc. Consistently, we observed that CX-5461 induced cell cycle arrest, and inhibited migration, invasion and EMT progression in CRC cells. Of note, the GSH, SLC7A11 and GPX4 were decreased in CX-5462 treated CRC cells, meanwhile ROS, MDA, and lipid ROS were increased. Furthermore, CX-5461 down-regulated Nrf2. Nrf2 activator THBQ successfully reversed the effect of CX-5461 on cell proliferation and ferroptosis. Mechanically, CX-5461 induces ubiquitinization of Nrf2. The decreased Nrf2 subsequently down-regulates SLC7A11 and GPX4. In conclusion, these results demonstrated that CX-5461 induced ferroptosis through inhibiting SLC7A11/GPX4 axis by promoting ubiquitinization of Nrf2 in CRC cells, suggesting that CX-5461 may be a valuable candidate for anti-cancer agent in CRC.

01 Sep 2025·Redox Biology

POLR1A inhibits ferroptosis by regulating TFAM-mediated mitophagy and iron homeostasis

Article

Author: Marti, Thomas M ; Zhou, Qinghua ; Vassella, Erik ; Yang, Zhang ; Dorn, Patrick ; Gao, Yanyun ; Harhai, Marcell ; Zhang, Tuo ; Jourdain, Alexis A ; Peng, Ren-Wang

Evasion of programmed cell death (PCD) is a hallmark of cancer, yet the mechanisms underlying resistance to ferroptosis - an iron-dependent form of PCD triggered by excessive lipid peroxidation - remain incompletely understood. Here, we identify a previously unrecognized nucleolar-mitochondrial signaling axis that promotes ferroptosis resistance in pleural mesothelioma (PM) and potentially other cancers. This pathway involves RNA polymerase I (PolI) catalytic subunit A (POLR1A) and mitochondrial transcription factor A (TFAM), which together regulate mitophagy and intracellular iron metabolism to suppress ferroptosis. Mechanistically, POLR1A controls TFAM expression via the transcription factor ATF4, and this POLR1A-ATF4-TFAM axis inhibits mitophagy and limit mitophagy-dependent labile Fe²⁺ release, thereby preventing Fe²⁺-driven lipid peroxidation. Disruption of this pathway through POLR1A or TFAM inhibition leads to Fe²⁺ accumulation and increased sensitivity to ferroptosis inducers (FINs). Notably, CX-5461, a first-in-class RNA PolI inhibitor currently in clinical trials, synergizes with GPX4 blockade to induce ferroptotic cell death both in vitro and in vivo. This therapeutic synergy extends beyond PM, suggesting broader relevance in ferroptosis-resistant cancers. Together, our findings reveal a novel mechanism of ferroptosis evasion and establish a promising combinatorial strategy to overcome therapy resistance in cancer.

01 Jul 2025·BIOCHIMIE

Ribosome biogenesis is a therapeutic vulnerability in pediatric neuroblastoma

Article

Author: Diaz, Jean-Jacques ; Combaret, Valérie ; Jouines, Camille ; Monet, Marie-Ambre ; Gaucherot, Angéline ; Simioni, Valentin ; Di Cacito, Isabelle Iacono ; Marcel, Virginie ; Monaco, Piero Lo ; Catez, Frédéric ; Monchiet, Déborah

Neuroblastoma is a heterogeneous malignant pediatric tumor, the prognosis of which depends on patient age and disease stage. Current treatment strategies rely on four key diagnostic criteria: age, histological stage, genomic profile, and MYCN gene status. The oncogenic activity of MYC depends on ribosome biogenesis, which is hyperactivated in cancer cells to support their high proliferative capacity, and which may thus represent a vulnerability in neuroblastoma and constitute a therapeutic target. Here, using the well-established IMR-32 cell line along with a previously established panel of patient-derived neuroblastoma cell lines with varying MYCN status, we show that RNA polymerase I inhibition following exposure to CX-5461 and BMH-21 suppressed cell proliferation at nanomolar concentrations and induced ribosomal stress, leading to the activation of apoptosis and the p21 pathway. Furthermore, analysis of expression of ribosome biogenesis factors using publicly available datasets and RT-qPCR data from an in-house neuroblastoma cohort, we identified FBL as a marker of poor prognosis in neuroblastoma. Consistently, FBL knockdown reduced neuroblastoma cell proliferation, supporting its relevance as a therapeutic target. In conclusion, our study reinforces the therapeutic potential of ribosome biogenesis inhibition in neuroblastoma and expands the list of potential targets to include rRNA maturation factors. These findings highlight the relevance of targeting ribosome biogenesis as a novel approach for neuroblastoma treatment.

News (Medical) associated with Pidnarulex

16 Jul 2025

·www.prnewswire.com

Senhwa Biosciences announces first patient dosed in NCI-sponsored pilot study of Pidnarulex (CX-5461) pharmacodynamics in patients with advanced solid tumors

TAIPEI and SAN DIEGO, July 15, 2025 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that its new drug Pidnarulex (CX-5461) has been selected by the U.S. National Cancer Institute (NCI) as part of a five-year cancer research program. The first patient in the monotherapy clinical trial for advanced solid tumors has been successfully enrolled at the NIH Clinical Center in Bethesda, Maryland, USA. The NCI will fund the full cost of the clinical trial—estimated at approximately USD 4.8 million. In addition to this initial monotherapy trial, three other cutting-edge clinical studies led and sponsored by NCI are in progress. These include combination therapies with immunotherapy, antibody-drug conjugates (ADCs), and a monotherapy study targeting MYC-driven lymphomas. IND submissions and patient enrollment for these additional studies are expected to begin shortly. Senhwa's broad collaboration with the NCI not only highlights the innovative potential of CX-5461 as a first-in-class molecule targeting novel cancer mechanisms, but also reflects international recognition of Taiwan's biotechnology achievements. This strengthens the company's visibility and strategic position on the global stage in oncology drug development. Trial Objectives and Research Focus The first trial in the NCI program will investigate CX-5461 as a single agent in patients with and without homologous recombination deficiency (HRD) gene mutations, evaluating its ability to induce the Rad51 response. The study also aims to identify additional biomarkers associated with synthetic lethality to help define patient populations more likely to respond to treatment and potentially expand its clinical indications. The trial plans to enroll 40 patients, with allocated resources including clinical site operations, pharmacokinetic (PK) and biomarker analyses, as well as execution costs such as regulatory compliance, data management, and electronic platform infrastructure. With full financial support from NCI, the trial is expected to save the company an estimated USD 4.8 million in clinical development costs, significantly reducing the R&D burden and accelerating the advancement of CX-5461. CX-5461 – A First-in-Class Investigational Drug CX-5461 is a first-in-class small molecule drug with a unique mechanism of action. It acts by selectively targeting and stabilizing G-quadruplexes (G4s), preventing their unwinding and triggering replication-dependent DNA damage, ultimately resulting in cancer cell apoptosis. The frequent presence of G4 structures in tumors, especially in transcriptionally active genes, implies their potential functional involvement in the development of cancer. By targeting G4s and triggering DNA damage in cancer cells, Pidnarulex (CX-5461) emerges as a potential therapeutic candidate with significant promise across multiple cancer indications. Growing Cancer Drug Market and the Need for Combination Therapies With global cancer incidence on the rise, particularly among younger populations, the market for oncology drugs continues to expand. Demand for immunotherapies—which activate the human immune system to fight cancer—remains strong. According to the latest report by Grand View Research, Inc., the global cancer immunotherapy market is projected to reach USD 224.3 billion by 2030, with a compound annual growth rate (CAGR) of 8.3% from 2024 to 2030. However, current immunotherapies benefit only around 20–25% of patients, creating an urgent need for combination therapies that modulate multiple pathways within the tumor microenvironment to enhance treatment efficacy. Senhwa is highly optimistic about its future clinical plans under the leadership of the NCI, particularly the combination studies involving CX-5461 and immunotherapies. These trials may help overcome the limitations of current immunotherapies and expand their benefit to a broader cancer patient population. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ImmunotherapyClinical StudyIND

25 Jun 2025

·www.prnewswire.com

Senhwa Biosciences Highlights Breakthroughs in Dual First-in-Class Drug Programs at Annual Shareholders' Meeting Today

TAIPEI and SAN DIEGO, June 25, 2025 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a clinical-stage biopharmaceutical company, held its 2025 Annual Shareholders' Meeting today, chaired by Chairman Mr. Benny T. Hu. The company delivered updates on its ongoing drug development programs, outlining four key strategic milestones poised to drive its transformative growth: Launch of a new HIV "Functional Cure" strategic program Advancement of partnership discussions with leading global immunotherapy companies Active negotiations of multiple licensing opportunities Dual-engine therapeutic breakthroughs from CX-4945 and CX-5461 Silmitasertib (CX-4945): Unlocking New Hope for HIV Cure In March, Senhwa made the strategic decision to discontinue its Community-Acquired Pneumonia clinical trial, prompting investor concern. This shift, based on compelling interim findings, redirected focus to the promising potential of CX-4945 in HIV treatment. Dr. Jason Huang, Acting CEO and Chief Medical Officer, revealed that in HIV-positive participants within the Community-Acquired Pneumonia study, a significant and rapid increase in a key immune biomarker was observed, potentially reflecting a marked restoration of previously impaired immune function. This finding suggests that CX-4945 may represent a novel therapeutic option and a new opportunity for those affected by HIV. At the same time, to address gastrointestinal side effects observed in previous studies, Senhwa is in the final stages of developing a new formulation of CX–4945. The updated formulation is designed to significantly reduce GI discomfort while also extending the compound's intellectual property protection for an additional 20 years, supporting both patient tolerability and long-term commercial value. The company is currently consulting with the U.S. FDA on its clinical development pathway and is planning a small-scale pilot study in Taiwan. The trial will focus on evaluating the combined effects of CX–4945 on latent HIV reactivation and immune enhancement. Given the lifelong adherence required by current HIV therapies, a successful approach incorporating CX-4945 could present a scalable and transformative path to functional cure for tens of millions of HIV patients worldwide. CX-4945 for Basal Cell Carcinoma (BCC): Strong Clinical Efficacy in Refractory Patients Recent trial results from CX-4945 in patients with advanced BCC who had failed standard and immunotherapy treatments showed highly encouraging outcomes. Among 25 evaluable patients: 3 achieved Partial Response (PR) and 10 achieved Stable Disease (SD). Two patients had Progression-Free Survival (PFS) exceeding 21 months. Senhwa is currently in active discussions with several potential collaborators. Pidnarulex (CX-5461): Broad-Spectrum Oncology Innovation As another globally first-in-class asset, CX-5461 is advancing through multiple clinical programs, including the NIH 5-Year Anti-Cancer Initiative and a trial in North America targeting solid tumors with specific genetic deficiencies (BRCA1/2, PALB2). In addition to a monotherapy study in late-stage solid tumors (HRD/non-HRD), the NIH NExT Program is preparing three other protocols: CX-5461 with immunotherapy for colorectal cancer, CX-5461 with ADC, now a major focus in oncology innovation, for breast cancer and CX-5461 monotherapy for MYC-driven lymphomas. All three projects are underway, with IND submissions and patient enrollment expected soon. Among North American patients in the ongoing trial, several have achieved PR or SD despite failing previous treatments. Most notably, a patient with pancreatic cancer, considered one of the most lethal and treatment-resistant malignancies, has survived over 22 months on CX-5461 while maintaining quality of life. This represents an extraordinary outcome in clinical oncology. Senhwa aims to complete enrollment and data analysis for this trial in 2026 and is concurrently evaluating out-licensing or joint development options. CX-5461 + Immunotherapy: A Dual-Engine Powerhouse CX-5461 uniquely reprograms the tumor microenvironment (TME) by activating tumor-infiltrating lymphocytes (TILs) and dendritic cells (DCs), converting "cold" tumors into "hot" tumors. This transformation significantly enhances the responses to immune checkpoint inhibitors (e.g., PD-1/PD-L1), which currently benefit only 20–30% of patients. Senhwa is planning clinical programs combining CX-5461 with immunotherapy across multiple cancers, including pancreatic cancer, head and neck cancer, and melanoma. The company is in strategic discussions with global immuno-oncology companies and aims to launch these studies in 2026, targeting a share of the multibillion-dollar global immunotherapy market. A Year of Execution and Transformative Progress Ahead From HIV to pancreatic cancer and beyond, Senhwa's multi-front strategy signals its commitment to addressing unmet medical needs. The management team expressed sincere gratitude to shareholders for their patience and continued trust, and reaffirmed its commitment to delivering on key milestones in the shortest possible time to realize the value of shareholder support. Senhwa is positioning itself as a global leader in next-generation therapeutics and a comprehensive solutions provider for unmet medical needs. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultImmunotherapyClinical StudyLicense out/in

14 Oct 2024

·www.prnewswire.com

US FDA issues Study May Proceed letter for the Pilot Study of Pidnarulex Pharmacodynamics in Patients with Advanced Solid Tumors, Sponsored by the US National Cancer Institute

TAIPEI and SAN DIEGO, Oct. 14, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that FDA issues Study May Proceed letter for its developing drug Pidnarulex (CX-5461) in trial entitled "Pilot Study of Pidnarulex Pharmacodynamics in Patients with Advanced Solid Tumors" sponsored by the US National Cancer Institute (NCI). The study will assess whether Pidnarulex (CX-5461) induces a Rad51 response, in patients with and without homologous repair deficiency (HRD) genetic mutations. This pilot study also aims to explore potential biomarkers beyond BRCA1/2 and PALB2 that may demonstrate synthetic lethality with Pidnarulex (CX-5461). The findings from this study may identify patients who are more responsive to Pidnarulex (CX-5461) treatment, potentially expanding its therapeutic applications, and may accelerate its path to market approval. In addition to this monotherapy trial, the NCI is considering future clinical trials involving Pidnarulex (CX-5461) in combination with other therapies, such as immunotherapies and antibody-drug conjugates (ADCs). Should these trials proceed as planned, they will be led by the NCI, utilizing its vast medical expertise, scientific resources, and regulatory experience—support that could significantly accelerate the development of Pidnarulex. Pidnarulex (CX-5461), developed by Senhwa, is a first-in-class small-molecule designed to stabilize G-quadruplex (G4) structures, which are frequently observed in promoters of oncogenes. By stalling replication fork progression, Pidnarulex induces DNA damage and promotes cancer cell death. Through this mechanism, Pidnarulex holds great potential as a therapeutic agent for various cancers. In recent years, immunotherapy has been the fastest-growing category in the cancer drug market. According to the 2023 global best-selling drug market analysis, the first PD-1 inhibitor Keytruda(Pembrolizumab), developed by Merck, topped the sales charts with $25.11 billion. Immunotherapy and cancer drugs account for nearly half of the market sales. International clinical research indicates that combined immunotherapy can enhance tumor response rates, reduce mortality, and prolong patient survival. Given that only 20% to 25% of patients benefit from effective immunotherapy, Senhwa expects that in future immuno-combination therapy trials, CX-5461 will change the tumor microenvironment with its innovative mechanism, thereby enhancing the efficacy of immunotherapy, realizing the corporate mission of bringing hope to life. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ImmunotherapyClinical Study

100 Deals associated with Pidnarulex

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Burkitt Lymphoma	Phase 2	-	National Cancer Institute	19 Sep 2025
High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements	Phase 2	-	National Cancer Institute	19 Sep 2025
Hematologic Neoplasms	Phase 2	Australia	-	12 Jan 2021
Ovarian Cancer	Phase 2	United States	Senhwa Biosciences, Inc.	10 Jan 2021
Breast Cancer	Phase 2	Canada	Senhwa Biosciences, Inc.	07 Sep 2018
Metastatic Solid Tumor	Phase 1	United States	National Cancer Institute	01 Jul 2025
Prostatic Cancer	Phase 1	United States	Senhwa Biosciences, Inc.	31 Oct 2022
Advanced Malignant Solid Neoplasm	Phase 1	United States	Senhwa Biosciences, Inc.	08 Sep 2021
Advanced Malignant Solid Neoplasm	Phase 1	Canada	Senhwa Biosciences, Inc.	08 Sep 2021
Liver metastases	Phase 1	Canada	Senhwa Biosciences, Inc.	13 Jun 2016

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04890613 (Phase Ib expansion study of CX-5461, ESMO2024)	Phase 1	Advanced Malignant Solid Neoplasm BRCA2 \| PALB2 \| BRCA1 ... View more	28	CX-5461 250 mg/m2	ziazdxpfuc(ctmzruyzwq) = 2 palmar-plantar erythrodysesthesia, 2 photosensitivity, 1 ocular photosensitivity; no grade 4 AE vmmhdwpbxv (jbabozaere ) View more	Positive	14 Sep 2024
NCT04890613 (Phase Ib expansion study of CX-5461, ESMO2024)	Phase 1		28	CX-5461 325 mg/m2		Positive	14 Sep 2024
NCT02719977 (Pubmed \| Nat Commun) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	40	CX-5461	xfqgvpvsqt(vgdmsqdyuo) = 475 mg/m2 days 1, 8 and 15 every 4 weeks lflnzvctlo (zqsgggihqp )	Positive	24 Jun 2022
SABCS2020	Phase 1	DNA Repair-Deficiency Disorders BRCA1/2 deficient \| HR-deficient tumors	40	CX-5461	yyjqnchdte(sllegaalwm) = dryznrzlkp kflnlufgcc (yubmhhqjca )	Positive	15 Feb 2020
ACTRN12613001061729 (ASCO2015)	Phase 1	Hematologic Neoplasms	13	CX-5461	qzjpnpnoyt(qxpgdnjypu) = Other adverse events (AEs) have been mild cytopenias related to underlying disease phfcwuldtf (vqjejjeqpv ) View more	-	20 May 2015

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