nibrozetone (RRx-001) / EpicentRx, SciClone - LARVOL DELTA

RRx-001 sensitizes triple-negative breast cancer cells to oxaliplatin through apoptosis, cell cycle arrest, and immune modulation. (PubMed, J Pharmacol Exp Ther) - "The use of this chemotherapy is diminished by the rapid emergence of resistance in tumor cells; this results in continued migration capability within tumor cells. RRx-001 addresses all oxaliplatin resistance mechanisms, and therefore may serve as an adjuvant therapeutic option for patients with triple-negative breast cancer."

Journal • Breast Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

RRx-001 induces apoptosis through reactive oxygen and endoplasmic reticulum stress in Burkitt lymphoma cells by acting as CD47 and c-Myc regulator. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "The overexpression of CD47 increases the proliferation and partially inhibits the apoptosis of BL cells induced by RRx-001. Hence, the findings of this study provided new evidence that RRx-001 may serve as a therapeutic drug for treating BL."

IO biomarker • Journal • Burkitt Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BAX • BCL2 • CASP8 • CASP9 • CD47 • MCL1 • MYC • XIAP

KEVLARx: RRx-001 for Reducing Oral Mucositis in Patients Receiving Chemotherapy and Radiation for Head and Neck Cancer (clinicaltrials.gov) - P2 | N=216 | Active, not recruiting | Sponsor: EpicentRx, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2025 ➔ Oct 2027 | Trial primary completion date: Jul 2025 ➔ Jul 2027

Enrollment closed • Trial completion date • Trial primary completion date • Mucositis • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

Validating novel therapeutic strategies and medical countermeasure for Parkinson’s disease linked to chemical exposures (WPC 2026) - "We are now progressing to in vivo rodent studies to assess the compound’s ability to mitigate behavioural impairments and neuropathological features characteristic of paraquat-induced PD-like neurodegeneration. If validated through translational research, RRx-001 holds promise as a disease-modifying agent with both preventive and therapeutic potential for PD and other neurodegenerative diseases."

CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CASP3 • CASP7 • IL1B • NLRP3

Validating the neuroprotective potential of RRx-001 in chemically induced neurodegeneration in Parkinson’s disease (WPC 2026) - "We are now extending this work to rodent models, assessing the efficacy of RRx-001 in mitigating behavioural and neuropathological phenotypes associated with manganese induced PD like neurodegeneration. If validated through translational research, RRx-001 could represent a disease-modifying therapeutic strategy with both prophylactic and interventional potential for PD and related neurodegenerative conditions."

CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • CASP3 • CASP7 • IL1B • NLRP3

Validating a neuroprotective medical countermeasure against chemical toxicant induced neurodegeneration in Parkinson’s disease (WPC 2026) - "Our results confirm that nanomolar doses of RRx-001 can exert robust neuroprotective effects against a diverse chemical toxicant linked to occupational exposure and military service, as well as idiopathic PD. These findings highlight its potential for development as a medical countermeasure for chemical exposures in military and occupational settings."

CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • CASP3 • CASP7 • IL1B • NLRP3

Increased antitumor activity and reduced organ toxicity of doxorubicin administered using RRx-001 modified RBCs (AACR 2025) - "For reference, a typical blood donation is approximately 450 mL. In conclusion, this describes the pre-clinical rationale and establishes a clinical procedure for administering RBCs loaded with doxorubicin and treated with RRx-001 as a way to improve its activity and reduce side effects."

Colorectal Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

RRx-001 inhibits G6PD to deplete NADPH and trigger disulfidptosis coupled with DAMP-mediated immunogenic cell death in hepatocellular carcinoma. (PubMed, Cell Death Discov) - "In vivo, RRx-001 significantly inhibits tumor growth, enhances T-cell infiltration, promotes M1 macrophage polarization, downregulates PD-L1 expression, and strengthens anti-tumor immunity through T cell-related pathways. With both metabolic and immunomodulatory effects, RRx-001 provides a basis for novel HCC therapies, and future research could explore its synergistic effects with immune checkpoint inhibitors."

IO biomarker • Journal • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • CD4 • CD8 • G6PD • HMGB1

Size-Transformable Supramolecular Nanoprodrugs Enable Redox Imbalance Amplification and Cholesterol Modulation to Boost Multidimensional Tumor Immunotherapy. (PubMed, Small) - "Nanoprodrugs orchestrate a sophisticated cascade of immune activation through four synergistic mechanisms: 1) size-switchable disassembly upon glutathione/ cholesterol exposure for deep tumor penetration; 2) redox imbalance driven by reactive nitrogen species accumulation and glutathione depletion via the synergistic action of oxaliplatin, ferrocene, and RRx-001 for ferroptosis augmentation; 3) immunogenic cell death induction via ferroptosis-apoptosis to initiate tumor immunity cycle, promoting T cell infiltration; and 4) T cell function reinvigoration with the downregulation of programmed cell death protein 1 and T-cell immunoglobulin 3 expression through cholesterol depletion in TME. This integrated approach achieved primary and distant tumor growth suppression, established durable immune memory against recurrence, and systemically enhanced the antitumor immunity. By concurrently targeting tumor immunogenicity, TME immunosuppression, and T cell exhaustion, this..."

IO biomarker • Journal • Oncology • PD-1

A multidimensional pan-cancer analysis of CD47 and its role in promoting malignant phenotype in pancreatic adenocarcinoma. (PubMed, Clin Transl Oncol) - "In conclusion, this study systematically characterizes the clinical and immunological associations of CD47 across multiple cancers and highlights its potential role in pancreatic adenocarcinoma, supporting the further investigation of CD47 as a therapeutic target."

IO biomarker • Journal • Pan tumor • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD47

RRx-001 ameliorates astrocyte pyroptosis by regulating LCN2-NLRP3 inflammasome activation in an MPTP-induced parkinson's disease mouse model. (PubMed, Cell Mol Life Sci) - "Furthermore, the 16 S rDNA analysis and metabolomic analysis of faecal pellets revealed that the intestinal tract of the RRx-treated PD mice presented a greater abundance of Deferribacterota at the phylum level than that of the PD model mice, and the gut microbiota metabolites and pathways were altered. Overall, the results of this study indicate that RRx has multiple effects on PD."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • LCN2 • NLRP3

pH-triggered Mn-ZIF8 nanoreactor enhances tumor immunotherapy by amplifying the cGAS-STING pathway through a self-reinforcing gas-metal synergy strategy. (PubMed, J Nanobiotechnology) - "In this study, we propose a Gas-Metal Synergy Strategy, which integrates immune activation and biosafety, by engineering a pH-responsive manganese-based zeolitic imidazolate framework (named MRPH) nanoplatform co-loaded with the nitric oxide (NO) donor RRX-001...Both in vitro and in vivo studies demonstrate that MRPH significantly enhances gas-amplified metalloimmunotherapy. This work pioneers a low-toxicity paradigm that integrates gas therapy and metal-based immunotherapy, offering a transformative approach to solid tumor immunotherapy."

Journal • Immune Modulation • Immunology • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD8

Validation of the clinical stage therapeutic agent RRx-001 as a novel disease-modifying treatment for Amyotrophic Lateral Sclerosis (Neuroscience 2025) - "Together, our results suggest that RRx-001 could be effective in slowing disease progression by blocking both pathological inflammasome activation, and independently, by increasing protective NRF2 in skeletal muscle, blood, and the central nervous system. Given that RRx-001 has been tested in over 300 patients to date, with no dose limiting toxicities or related serious adverse events, our results highlight the prospect of RRx-001 as a new disease-modifying therapeutic for ALS with the potential for rapid clinical translation."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • NLRP3

Dual STING activation and CD47/SIRPα blockade via chitooligosaccharide-based nanoparticles to amplify antitumor immunity. (PubMed, J Control Release) - "To further counter immune evasion, we encapsulated the CD47/SIRPα inhibitor RRX-001 into reactive oxygen species (ROS)-responsive carriers, yielding [email protected] CT26 tumor-bearing mice, RRX@RCD achieved superior tumor regression, doubled median survival. Overall, RRX@RCD synchronizes innate and adaptive immune activation, offering a safe and potent nanomedicine strategy for durable antitumor immunity."

IO biomarker • Journal • Oncology • CD8 • CXCL10 • SIRPA • STING

Enhancement of Targeted and Antitumor Effects of M1 Macrophages Based on Bioorthogonal Reactions. (PubMed, Mol Pharm) - "Addition of the small-molecule inhibitor RRx-001 further improved the synergistic effect on phagocytosis and immune cell phenotypes in tumors. In summary, our study highlights the metabolic labeling strategy as a potent approach to promote M1 macrophage-mediated antitumor responses within the tumor environment, providing a novel means for the development of therapeutic strategies tailored for solid tumors."

Journal • Oncology • Solid Tumor

Signal Transducer Nanoparticles Enable Siglec-10/G Blockade Immunotherapy for Breast Cancer Treatment. (PubMed, Adv Mater) - "The therapeutic effects can be further improved through encapsulation of RRx-001, a small molecule inhibitor of the CD47-SIRPα signaling. Compared to the antibody approach, the synthetic nanoparticle approach offers greater efficacy with lower side effects and enables combination therapy through a simple formulation. Moreover, the approach is versatile and could be adapted for targeting other ICB signaling, advancing the next generation of cancer immunotherapy."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD24 • SIRPA

Biomimetic Delivery of Cisplatin for Efficient Immunotherapy of Gasdermin E-Positive Hepatocellular Carcinoma via a Pt Concentration-Dependent Minimalist Pyroptosis Strategy. (PubMed, Adv Healthc Mater) - "Compared to the classical Gasdermin D (GSDMD)-mediated pyroptosis that has been extensively explored for cancer immunotherapy, the direct induction of Gasdermin E (GSDME) pyroptosis has been rarely reported, likely due to the well-recognized reduced GSDME levels in solid tumors. This nanoplatform, CDDP/1-bromoacetyl-3,3-dinitroazetidine (RRx-001) @iRGD-Pla-Exo nanoparticles (CRRPE NPs) leads to almost complete tumor eradication in a Hepa1-6-luc orthotopic liver cancer model by activating macrophages, and can be combined with the commercially available programmed death ligand 1 (PD-L1) antibody immunomodulator to maintain T cells' effector function for a prolonged survival lifetime. Overall, this study provides a conceptual advance in revealing the role of chemotherapy in mediating tumor cell pyroptosis and immune cell activation."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • GSDME

RRx-001, A Specific Macrophage-Targeted Immunotherapeutic, Orchestrates a Cd45+ Anti-Endometriosis Impact (WCE 2025) - "RRx-001 minimally impacts the endometrium, supporting our previous findings of unaffected fertility. Taken together, RRx-001 represents a promising new therapy for endometriosis and is soon to enter a clinical trial."

IO biomarker • Endometriosis • Gynecology • Pain • Women's Health • PTPRC

Therapeutic Hypothermia and Recombinant Erythropoietin Mitigate Brain Microvascular Endothelial Cell Dysfunction via Modulating the Pentose Phosphate Pathway. (PubMed, J Mol Neurosci) - "Human brain microvascular endothelial cells (HBMECs) underwent oxygen-glucose deprivation (OGD) and were treated with TH and G6PD inhibitor RRx-001...Inhibition of G6PD disrupted the protective effects of TH and EPO on the patency of the PPP and the function of HBMECs, and barrier integrity was further broken. This study reveals that the combination of TH and EPO mitigates microvascular endothelial cell dysfunction via partially modulating the PPP, thus preserving barrier integrity."

Journal • CNS Disorders • Inflammation • Vascular Neurology

Innate immune checkpoint SIRPα/CD47 blockade ameliorates silica-induced pulmonary fibrosis by modulating macrophage immunity. (PubMed, Int Immunopharmacol) - "Using RRx-001 to block SIRPα/CD47 signaling in mice, we observed a marked reduction in lung injury, decreased collagen deposition, and improved pulmonary function...Additionally, levels of soluble SIRPα and CD47 in the peripheral blood of silicosis patients were significantly higher than those in healthy controls. In summary, this study demonstrates that SIRPα/CD47-mediated immunomodulatory signaling is the driving factor for the progression of silicosis, and this pathway might serve as a therapeutic target for silicosis treatment."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CD47 • SIRPA

Nitro-group π system drives the interaction of RRx-001 with solvated electrons in solution. (PubMed, Chemistry) - "Surprisingly, no Br dissociation is observed despite its high electron affinity. We assign this behavior to the "inaccessibility" of sigma virtual states for electrons in the solvent, which can be of a general nature."

Journal

Rational design of alternative treatment options for radioresistant rectal cancer using patient-derived organoids. (PubMed, Br J Cancer) - "Combining RRx-001 with the inhibition of GCLC may be a promising alternative treatment strategy in radioresistant rectal cancer."

Journal • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

Orphan Drug Designations and Approvals (FDA) - "Generic Name: N-(bromoacetyl)-3,3-dinitroazetidine; Date Designated: 06/15/2017; Orphan Designation: Treatment of neuroendocrine tumors; Orphan Designation Status: Designated"

Orphan drug • Neuroendocrine Tumor

EpicentRx and Texas Children's Cancer Center Announce the Initiation of a Phase 1 Clinical Trial with RRx-001 for Pediatric CNS Tumors (PRNewswire) - "EpicentRx, Inc...today announced the start of a Phase 1 study to examine the safety and benefit of its lead small molecule, RRx-001, plus irinotecan and temozolomide for pediatric patients with recurrent or progressive malignant solid and central nervous system tumors. The study, PIRATE (NCT04525014) was conceived and developed by doctors Holly Lindsay and Patricia Baxter at the Texas Children's Cancer Center and will enroll patients 1 to 21 years of age with recurrent or progressive malignant primary brain or spinal cord tumors and solid tumors, excluding lymphomas."

New P1 trial • Brain Cancer • CNS Tumor • Oncology • Solid Tumor

Chimeric Peptide Functionalized Immunostimulant to Orchestrate Photodynamic Immunotherapeutic Effect by PD-L1 Deglycosylation and CD47 Inhibition. (PubMed, ACS Appl Mater Interfaces) - "Concurrently, the release of RRx-001 blocks the CD47 pathway, disrupting the antiphagocytic signaling of breast cancer cells and activating innate immune responses. This synergistic immunomodulatory approach effectively reverses the complex immunosuppressive factors, significantly enhancing the immunotherapeutic effects of conventional treatments."

Journal • Breast Cancer • Oncology • Solid Tumor