pidnarulex (CX-5461) / Senhwa Biosci - LARVOL DELTA

Enhancing CX-5461 therapy in TNBC through liposomal delivery and ATR inhibitor combination (AACR 2026) - "CX-5461 is a promising agent for DNA repair-deficient TNBC, with strong single-agent activity demonstrated in vitro and in vivo. Preliminary combination studies with Berzosertib revealed synergistic potential. Future in vivo studies will evaluate whether liposomal delivery and combination therapy can improve survival in TNBC."

Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HRD

EWSR1::FLI1 suppresses ribosome biogenesis and creates a targetable vulnerability in Ewing sarcoma (AACR 2026) - "Moreover, etoposide treatment selectively triggers SLFN11-dependent translational shutdown in EwS cells, in addition to inducing DNA damage, highlighting its dual impact on both the genome and the already fragile translational machinery. Finally, CX-5461 demonstrated potent therapeutic activity with evidence of synergistic effects when combined with the PARP inhibitor Olaparib selectively in EwS, warranting further investigation of rational combination strategies. Together, our findings reveal that reduced ribosome biogenesis - rather than its hyperactivation - is an important feature of EwS and creates a distinct therapeutic vulnerability. Targeting this constraint offers a promising new strategy for a disease that currently lacks effective targeted therapies."

Tumor mutational burden • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • EWSR1 • FLI1 • SLFN11 • TMB

Breakthrough at 2026 AACR! Senhwa Biosciences' CX-5461 Enters the Field of Photodynamic Therapy, Opening a New Indication Strategy (The Manila Times) - "The pre-clinical study shows that CX-5461 possesses photosensitizing properties. When exposed to ultraviolet (UV) light, the compound generates reactive oxygen species (ROS), leading to oxidative DNA damage and enhanced cancer cell death through both direct cytotoxicity and immune-mediated mechanisms. Under the same drug concentration conditions, cytotoxicity against cancer cells increased by approximately ten-fold...Further investigation revealed that CX-5461's binding to G-quadruplex (G4) DNA structures works synergistically with light-induced ROS generation, significantly enhancing anti-tumor activity and prolonging survival."

Preclinical • Solid Tumor

CX-5461 exerts pangenotypic anti-hepatitis E virus effect in preclinical models (EASL 2026) - No abstract available

Preclinical • Hepatology • Inflammation

In vivo CRISPR knockout screen reveals ribosome biogenesis as a driver and a potential therapeutic target for melanoma metastasis. (AACR 2026) - "Importantly, pharmacological inhibition with CX-5461 (Polr1 inhibitor) significantly slowed down the primary tumor growth and dramatically decreased the number of lung metastases...Indeed, western blot analysis of the cells with Polr1a KD confirmed that a decrease in Polr1a level is associated with the decrease of p52 and ReIB, which are the key proteins responsible for the activation of the non-canonical NF-κB pathway. Re-expression of RelB in the cells with Polr1a KD rescued the migration phenotype, demonstrating that Polr1a regulates melanoma migration ability in an NF-κB-dependent manner.Overall, these results suggest Polr1a as a prospective new target for the treatment of metastatic melanoma and shed light on a potential mechanism responsible for the pro-metastatic effect of this gene."

Preclinical • Melanoma • Oncology • Solid Tumor • RELB

Combinatorial profiling of pidnarulex and other G-quadruplex ligands in 3D multicellular tumor spheroids (AACR 2026) - "To assess the therapeutic potential of three G4 ligands—pidnarulex, APTO-253, and BRACO-19—we performed a high-throughput drug-combination screen across thirty-one multicellular tumor spheroids derived from patient tumors and established cancer cell lines. This project was funded with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024."

Oncology • Pancreatic Adenocarcinoma • PIM1

(E,E)-bisantrene silences c-MYC expression by stabilizing its promotor region G-quadruplex (AACR 2026) - "(E,E)-bisantrene binds to and stabilizes the G4 structure contained within the c-MYC promotor region, leading to silencing of c-MYC gene expression. These studies support clinical evaluation of (E,E)-bisantrene as a new G4-targeting drug in MYC-driven tumors."

Oncology • ATF4 • MYC

Pilot study of pidnarulex pharmacodynamics in patients with advanced solid tumors (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Metastases • PK/PD data • Oncology • Solid Tumor

Photodynamic activation of CX-5461 enhances its anti-tumor efficacy (AACR 2026) - "CX-5461 is a photosensitizer that produces both type I and type II ROS, which increases its cytotoxic effects in vitro when exposed to UV light. The efficacy of CX-5461 in combination with UV treatment has been demonstrated in syngeneic models like CT26 and B16F10. These findings suggest that the phototoxic properties of CX-5461 could represent a novel therapeutic strategy for treating of cancers that are amenable to UV light exposure."

Clinical • Oncology • Ovarian Cancer • Solid Tumor

PMR-116, a second-generation RNA polymerase I inhibitor displaying therapeutic efficacy in a broad spectrum of malignancies (AACR 2026) - "First-generation Pol I inhibitor CX-5461 showed clinical benefits but also triggered non-specific DNA damage. No global DNA damage signalling was detected at active dose levels.Overall, PMR-116 shows potent anti-cancer activity across a wide range of malignancies, with particular strength in MYC-driven tumours. Its selectivity for Pol I and favourable safety profile support its progression into an MRFF-funded phase II basket trial commencing in 2026."

Clinical • Breast Cancer • Colorectal Cancer • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor • MYC • NRAS • TP53

G-quadruplex stabilization enhances chemosensitivity in endometrial cancer via autophagy modulation (ESGO 2026) - "Furthermore, combining carboplatin with either G4 ligand synergistically increased tumor cell death in PDOs compared to monotherapy, as demonstrated in live/dead viability assays.Conclusion These findings demonstrate that G4 stabilization triggers a protective autophagy program in EC cells, while inhibition of autophagy redirects cells toward apoptosis. Co-targeting G4 DNA and autophagy—alongside platinum-based chemotherapy—may therefore represent a promising strategy to overcome therapeutic resistance in aggressive EC.Given that CX-5461 has received FDA fast-track designation and is currently in Phase I clinical trials for DNA-repair-deficient malignancies, these results hold immediate translational relevance."

Endometrial Cancer • Oncology • Solid Tumor • ANXA5 • CASP3 • CASP7

RNA polymerase I inhibitor CX-5461 suppresses cervical cancer cell growth by inducing DNA damage and mitotic catastrophe and enhances cisplatin sensitivity. (PubMed, Biochem Pharmacol) - "When combined with cisplatin, CX-5461 enhances the sensitivity of cervical cancer cells to this chemotherapeutic agent. In conclusion, CX-5461 demonstrates potential therapeutic value for cervical cancer, particularly as a new strategy for patients with primary or platinum-resistant disease."

Journal • Cervical Cancer • Oncology • Solid Tumor • CCNB1 • CDK1

TFEB confers resistance against the chemotherapeutic agent CX-5461. (PubMed, Autophagy Rep) - "Interfering with TFEB improved the sensitivity of cancer cells to both CX-5461 and gemcitabine. Our findings suggest that TFEB provides broad protection against the stress caused by chemotherapeutic drugs, representing a promising target for intercepting chemoresistance and improving the efficacy of anticancer agents."

Journal • Oncology • TFEB

Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2026 ➔ Oct 2026

Enrollment open • Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Testing the Safety of Anti-Cancer Drug, CX-5461 (Pidnarulex), in Treating Lymphoma With Specific Changes in the MYC Gene (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2027 ➔ Jan 2030 | Initiation date: Mar 2026 ➔ Oct 2026 | Trial primary completion date: Sep 2027 ➔ Jan 2030

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • B Cell Lymphoma • Burkitt Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

Moonlighting function of the GTP producing enzyme IMPDH2 in melanoma suppression (LCC 2026) - "P53 activation by CX5461, H2O2 or Nutlin-3 led to nuclear translocation of IMPDH2, but this effect was fully abrogated by p53 CRISPR-KO...CDK2 inhibition by INX315 or CDK2 silencing dramatically reduced S122 phosphorylation and induced nuclear translocation of IMPDH2...In contrast, nuclear IMPDH2 acts as a tumour suppressor to repress transcription of E2F target genes and induce CDK inhibitor genes leading to cell cycle arrest and senescence. Increasing IMPDH2's N/C ratio in melanoma cells by targeting its S122 phosphorylation is a promising therapeutic strategy."

Melanoma • Solid Tumor • IMPDH2

Targeting the nucleoli as a strategy to treat ovarian cancer (LCC 2026) - "Inhibitors of Pol I transcription CX-5461, BMH-21 and PMR116 have demonstrated therapeutic benefits in various preclinical cancer models and in Phase I clinical trials. Cyclin dependent kinases (CDKs), topoisomerases and novel compounds were identified as candidate hits that induce potent nucleolar stress. In summary, our work uncovered specific pathways/factors as mediators of nucleolar stress and potential cancer therapeutic targets."

Oncology • Ovarian Cancer • Solid Tumor

Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies. (PubMed, Nat Commun) - P1 | "These results establish clinical proof-of-concept for this G-quadruplex stabilizer. Clinicaltrials.gov NCT02719977."

Journal • P1 data • Oncology • Solid Tumor • BRCA2 • DRD • HRD • PALB2

CX-5461 and Doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes. (PubMed, G3 (Bethesda)) - "Micromolar CX concentrations affect heart-specific genes and 14 functionally-validated genes in loci associated with DOX cardiotoxicity. Our data demonstrate the impact of CX on the transcriptome of cardiomyocytes, a potential off-target cell type of the drug."

Journal • Cardiovascular • Oncology

Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2027 ➔ Jan 2028 | Trial primary completion date: Mar 2027 ➔ Jan 2028

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Senhwa Biosciences Aims at Multi-Billion Dollar Global Market with CX-5461 Combined with ADC "Blockbuster" Therapy (PRNewswire) - "The Company's first-in-class investigational drug Pidnarulex (CX-5461) will be evaluated in combination with the globally recognized antibody-drug conjugate (ADC), Trastuzumab Deruxtecan (Enhertu), in a Phase 1b clinical trial. The study is designed for HER2-positive solid tumors and breast cancer patients, including those with HER2-low expression and metastatic breast cancer. Supported by the U.S. National Cancer Institute's (NCI) NExT program, which funds multiple CX-5461 studies including combination strategies, Senhwa is positioning itself at the forefront of one of the most promising areas in oncology therapeutics, and this milestone marks CX-5461's entry into the fast-growing ADC market."

New P1 trial • HER2 Breast Cancer • HER2 Positive Breast Cancer • Solid Tumor

Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Dec 2025 ➔ Mar 2026

Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Testing the Effectiveness of the Anti-cancer Drug Pidnarulex (CX-5461) in Combination With Another Anti-cancer Drug Cemiplimab (REGN2810), in Treating Refractory Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=86 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Dec 2025 ➔ Mar 2026

Trial initiation date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

Testing the Safety of Anti-Cancer Drug, CX-5461 (Pidnarulex), in Treating Lymphoma With Specific Changes in the MYC Gene (clinicaltrials.gov) - P1/2 | N=50 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Dec 2025 ➔ Mar 2026

Trial initiation date • B Cell Lymphoma • Burkitt Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

Targeting RNA Polymerase I Inhibits Ribosome Biogenesis to Block Liver Fibrosis Progression. (PubMed, Liver Int) - "Pol I-regulated ribosome biogenesis is significantly increased during HSCs activation and liver fibrosis progression. Pol I may serve as a potential target for the diagnosis and treatment of liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • TGFB1