Tirazone (tirapazamine) / Teclison, SRI International - LARVOL DELTA

A hypoxia-activated and tumor microenvironment-remodeling nanoplatform for augmenting sonodynamic-chemodynamic-chemotherapy of breast cancer. (PubMed, Biomater Sci) - "The innovative Lip-Ce6-MnO2-TPZ nanoparticle was constructed by loading Ce6, MnO2, and hypoxia responsive drug tirapazamine (TPZ) together into a cytotoxic reactive oxygen species (ROS) responsive nanocarrier...Overall, the Lip-Ce6-MnO2-TPZ platform could induce the generation of excess ROS combined with antioxidant depletion, resulting in oxidative stress and aberrant redox homeostasis of the TME. This strategy has brought forward the idea of inducing cancer cell death by synergistically working SDT, CDT, and hypoxia-activated prodrugs to maximize the therapeutic efficacy in cancer treatment."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor

Phosphorous dendrimer-mediated biomineralization for synergistic blockade therapy and hypoxia-activated chemotherapy of tumors. (PubMed, Acta Biomater) - "Herein, we report the phosphite-terminated phosphorus dendrimers (AK176)/fibronectin (FN) nanocomplexes (NCs) with tumor-targeting and biomineralization-inducing properties to encapsulate a hypoxia-activated tirapazamine (TPZ) to achieve synergistic blockade therapy/chemotherapy of triple-negative breast cancer (TNBC)...The developed AK176@FN/TPZ (AFT) NCs can target tumor cells through specific recognition between the Arg-Gly-Asp sequence of FN and αvβ3 integrin receptors, and specifically induce mineral deposition via the inherent calcium ion adsorption property of bisphosphonate groups of dendrimers, thereby triggering tumor biomineralization for blockade therapy. The AFT-mediated biomineralization on tumor cell membranes generates tumor hypoxia, which further amplifies the chemotherapeutic effect of TPZ."

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

Multifunctional Mesoporous Silicon Nanoparticles for MRI-Based Diagnostic Imaging and Glioma Therapy. (PubMed, ACS Appl Mater Interfaces) - "This system integrates tirapazamine (TPZ), glucose oxidase (GOx), in situ-synthesized copper sulfide (CuS), and CT2A glioma cell membrane coating to enable dual tumor-targeted therapy and self-imaging capabilities...Experimental results demonstrated that HCTG-C achieves real-time MRI monitoring via GSH depletion-driven Cu valence transitions, while its self-replenishing H2O2 and oxygen-activation mechanisms significantly enhance antitumor efficacy against CT2A glioma in vitro and in vivo. By innovatively combining H2O2 self-supply cascades, hypoxia-activated chemotherapy, and ferroptosis-driven CDT, this work presents a paradigm-shifting strategy for self-imaging-guided combinatorial therapy, advancing ferroptosis-based approaches for precision glioma treatment."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Sulforaphane enhances cytototoxic effects of novel non-thermal plasma and Tirapazamine combined therapy in pancreatic adenocarcinoma cells (AACR 2025) - "However, the Western blots show inconsistent loss of vimentin, consistent loss of E-cadherin, and no upregulation of Cx43. While these results suggest SF has potential as an adjunct agent, further investigation is needed to understand the causes of increased cytotoxicity between SF and NTP+TPZ in pancreatic adenocarcinomas."

Brain Cancer • CNS Tumor • Glioblastoma • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CDH1 • VIM

Construction of a programmed activation nanosystem based on intracellular hypoxia in cisplatin-resistant tumor cells for reversing cisplatin resistance. (PubMed, Mater Today Bio) - "The cisplatin-resistant tumor cell specific intracellular hypoxia programmed activation nanomedicine (T/C@HN NPs) was constructed by the hypoxic toxic drug tirapazamine (TPZ) and encapsulating chlorin e6 (Ce6) into HA-NI using polymer assembly technology. This project systematically evaluated the effects of T/C@HN NPs on the identification and recognition of cisplatin-resistant tumors using drug-resistant patient-derived xenograft (PDX) models. This study provides a promising avenue for the development of novel treatment of cisplatin-resistant tumors."

Journal • Oncology

Synergistic Comprehensive Activation Methods for Dual-Modality PDT and Hypoxia-Triggered Chemotherapy Guided by NIR-II Imaging beyond 1700 nm in Deep Tumors. (PubMed, Small) - "Moreover, PDT aggravates tumor hypoxia, which in turn activates the hypoxia-activatable prodrugs like tirapazamine, resulting in a synergistic antitumor effect. With NIR-IIc imaging-guided dual-modality PDT, this study introduces a groundbreaking approach that unites Type I/II PDT with chemotherapy, significantly advancing the precise and effective treatment of deep hypoxic tumors."

Journal • Oncology

A Phase II/III Trial Comparing Transarterial Tirapazamine Embolization (TATE) With cTACE for Intermediate-stage Liver Cancer. (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Porphyrin-based covalent organic framework with NIR absorption: Preparation, hyaluronic acid modification, and cascading a hypoxia-sensitive drug for synergistic therapy of cancer phototherapy/chemotherapy. (PubMed, Int J Biol Macromol) - "Second, the hypoxia-responsive drug tirapazamine (TPZ) and tumor-targeted hyaluronic acid (HA) were loaded to Por-COF through the electrostatic effect to prepare a multifunction nanomedicine (Por-COF@TPZ/HA) that could simultaneously produce abundant reactive oxygen species and high temperature via808 nm laser irradiation...Combined photodynamic-photothermal therapy and chemotherapy had an outstanding synergistic effect. This work provides a promising method for Por-COF preparation and a feasible strategy for the synergistic therapy of cancers."

Journal • Oncology

5-Aminolaevulinic Acid-Mediated Photodynamic Therapy Combined with Tirapazamine Enhances Efficacy in Ovarian Cancer. (PubMed, Biomedicines) - "The enhanced therapeutic effect may be attributable to the inhibition of the hypoxia-inducible factor-1α/vascular endothelial growth factor axis and PI3K/Akt/mTOR pathway. 5-ALA-PDT combined with TPZ can overcome both the hypoxic state of ovarian cancer tissues and the increased hypoxia induced by PDT, thereby inhibiting tumour growth."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • HIF1A

Effect of conventional physiotherapy versus strain counter for trapezitis patients. (PubMed, Bioinformation) - "We found that, group 2 showed significant improvements in range of motion, pain and neck disability outcome scores. Thus, that SCS can be used as a low-cost and effective treatment for trapezitis."

Journal • Musculoskeletal Pain • Pain

Nanocapsules with dual-targeting of cell and mitochondria functions for enhanced hypoxia-activated drug therapy. (PubMed, Chem Commun (Camb)) - "The cell and mitochondria dual-targeting nanocapsules reported here could exacerbate tumor hypoxia to activate a hypoxia-activated drug, tirapazamine, producing benzotriazinyl radicals and ˙OH, which are capable of killing tumor cells via DNA damage. In addition, mitochondrial dysfunction can result from the accumulation of ˙OH. This chain reaction triggers a surge in ROS that can effectively increase the therapeutic efficiency of the nanocapsules."

Journal • Metabolic Disorders • Oncology

Coenzyme Q10 as an Inhibitor of Effector Release from One-Electron-Reduced Bioreductive Anticancer Prodrugs. (PubMed, Molecules) - "Evidence is put forward suggesting that radical anions can undergo an electron transfer to ubiquinone (CoQ10, UQ) in competition with the fragmentation of the radical anions releasing effectors. The prior inhibition of the synthesis of UQ in cells is put forward as a possible approach to increase the effectiveness of such prodrugs in killing hypoxic tumor cells."

Journal • Oncology

A Phase II/III Trial Comparing Transarterial Tirapazamine Embolization (TATE) with CTACE for Intermediate-stage Liver Cancer. (clinicaltrials.gov) - P2/3 | N=300 | Not yet recruiting | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

New P2/3 trial • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Evaluate the Effect of Tirazamine on Primary Liver Cancer. (clinicaltrials.gov) - P1/2 | N=16 | Terminated | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

New P1/2 trial • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Tumor Microenvironment-Responsive Nanodrug for Embolotherapy and Enhanced Chemotherapy. (PubMed, ACS Appl Mater Interfaces) - "This study presents a mesoporous polydopamine-based (MPDA) drug delivery platform modified by engineered fusion proteins, which can specifically embolize tumor blood vessels and deliver the hypoxia-activated prodrug tirapazamine (TPZ)...This nanodrug can actively target HER-2, interact with MMP-2 in the tumor microenvironment (TME), and embolize blood vessels; then, under TME acidic circumstances, MPDA releases TPZ, which is activated by hypoxia aggravated by embolization, and kills tumors. This embolization strategy, which is activated only under specific conditions, is extremely safe, and it compensates for the inadequacies of conventional embolization therapy, while also addressing the issue of hypoxia deficiency in hypoxia-activated prodrug therapy."

Biomarker • Journal • Oncology • MMP2

TATE and KN046 in MCRC (clinicaltrials.gov) - P2 | N=42 | Terminated | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

New P2 trial • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

Hypoxia-driven mobilization of altruistic cancer stem cells in platinum-treated head and neck cancer. (PubMed, Front Immunol) - "These cells displayed increased proliferation and invasion upon cisplatin treatment, suggesting a role in niche defense...Notably, inhibiting hypoxia alone with tirapazamine did not reduce TSD+ CSCs, CTCs, or R-CSCs...Additionally, the pre-clinical study provides a novel non-genetic mechanism of therapy resistance-the altruistic tumor self-defense. The tumor microenvironment, through the emergence of TSD+ CSCs, appears to act collectively to defend the tumor self-identity by hijacking an altruistic stem cell niche defense mechanism."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EPAS1

Optimizing interventional therapy: A homogeneous lipiodol formulation of Tirapazamine and Sorafenib responsive to post-embolization microenvironment. (PubMed, J Control Release) - "In summary, this study developed a novel embolization drug formulation based on embolic hypoxic microenvironment. The synergistic mechanism of TPZ and SFB enhances the therapeutic effects of hypoxia-activated prodrugs and mitigates the adverse effects of hypoxia."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Hypoxia-Targeted-Therapy: Mussel-inspired hollow polydopamine nanocarrier containing MoS2 nanozyme and tirapazamine with anti-angiogenesis property for synergistic tumor therapy. (PubMed, J Colloid Interface Sci) - "In vivo studies in 4T1-tumor-bearing mice confirm that HPTZMoS NBs induces significant tumor destruction through a combination of PTT, hyperthermia-induced CDT, GT, and CT pathways. This study presents a multifaceted, highly selective nanotherapy platform with potent anti-angiogenesis properties, holding significant promise for future clinical applications."

Journal • Oncology

Mannose functionalized small molecule nanodrug self-assembled from amphiphilic prodrug connected by disulfide bonds for synergistic cancer chemotherapy and photodynamic/photothermal therapy. (PubMed, Int J Pharm) - "The hydrophobic hypoxic-activated agent tirapazamine (TPZ) and a hydrophilic fluorescence probe Cyanine 3 (Cy3) constitute this amphiphilic prodrug via a glutathione (GSH)-responsive linkage, which could self-assemble into stable nanoparticles (NPs) and encapsulate a newly synthesized photosensitizer (SeBDP)...Our findings demonstrate that SeBDP@TPZ-S-S-Cy/Man NPs have great potential for enhancing cancer treatment both in vitro and in vivo by combining an oxygen depletion prodrug with a hypoxia-activated antitumor agent. Thus, the GSH-sensitive self-assembled nanodrug from an amphiphilic hypoxia-activated prodrug, could serve as a potential drug carrier in targeted synergistic cancer therapy."

Journal • Oncology

Biomimetic Diselenide-Sonosensitizer Nanoplatform for Enhanced Sonodynamic Therapy and In Situ Remodeling Immunosuppressive Microenvironment via Activating Innate and Adaptive Immunotherapy. (PubMed, Adv Healthc Mater) - "To alleviate these challenges, we proposed the development of a multifunctional biomimetic nanoplatform (mTSeIR), which was designed with diselenide-conjugated sonosensitizers and tirapazamine (TPZ), encapsulated within M1 macrophage membrane...Ultimately, in vivo studies indicated that mTSeIR+US with good biosafety achieved over 98% tumor inhibition and enhanced adaptive immunotherapy. This research presents an efficient approach that addressed the limitations of SDT and achieves simultaneous activation of both innate and adaptive immunotherapy, resulting in significant antitumor and anti-metastatic efficacy in TNBC."

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

Higher Tumor/Organ Accumulation Ratio of Porous Dual Infinite Coordination Polymer Nanocomposites for Efficient Tumor Photothermal-Starvation-Dual Hypoxia Chemo Synergistic Therapy. (PubMed, Small) - "To enhance tumor comprehensive therapeutic effect of nanomedicines, an efficient strategy that integrates polydopamine and IR780 photothermal therapy, glucose oxidase (GOx) starvation therapy, Banoxantrone (AQ4N) and Tirapazamine (TPZ) dual hypoxia chemotherapy is developed in chronological order...Then AQ4N and TPZ undergo synergistic chemotherapy in the enhanced hypoxic environment. Animal experiments show a tumor inhibition rate of 100% and a tumor recurrence rate of 0% after 60 d, demonstrating their great potential application for tumor treatment."

Journal • Oncology

Transferrin Protein Corona-Targeted Codelivery of Tirapazamine and IR820 Facilitates Efficient PDT-Induced Hypoxic Chemotherapy on 4T1 Breast Cancer. (PubMed, ACS Appl Mater Interfaces) - "IR could kill tumors through photodynamic therapy (PDT) and elicit complementary antitumor effects with the hypoxia-sensitive drug TPZ. This study demonstrates the novel design of in situ PC-mediated multifunctional liposomes for hypoxia-activated chemotherapy combined with PDT, a promising approach to cancer therapy."

Journal • Breast Cancer • Oncology • Solid Tumor

TATE-PD1: Combination of TATE and PD-1 Inhibitor in Liver Cancer (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: Teclison Ltd. | Phase classification: P2a ➔ P2 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Metastases • Phase classification • Trial primary completion date • Gastric Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Hypoxia-activated prodrugs with distinct mechanisms of action sensitize murine prostate tumors to immune checkpoint blockade (SITC 2024) - "Targeting hypoxia using the hypoxia-activated prodrug (HAP), evofosfamide (TH-302; IMGS-101) reduced hypoxic regions and co-operated with immune checkpoint blockade (ICB) (anti CTLA-4+anti PD-1) to drive tumor regression in transplantable and spontaneous murine prostate tumors.4 In a Phase I clinical trial, combination of evofosfamide and anti CTLA-4 (Ipilimumab) elicited both objective response and prolonged disease stabilization in patients who had failed other forms of therapy.5 While evofosfamide has shown promising results in preclinical and clinical settings, it is unknown whether hypoxia reduction is a unique property of evofosfamide or if HAP with distinct mechanisms of action could achieve comparable therapeutic efficacy. Methods We investigated the efficacy of evofosfamide, AQ4N (Banoxantrone) and TPZ (Tirapazamine), three HAP with distinct mechanisms of action, for their ability to reduce tumor hypoxia, drive tumor regression and sensitize murine prostate..."

Checkpoint block • Checkpoint inhibition • Preclinical • Melanoma • Oncology • Prostate Cancer • CD4 • CD8