Triapine (3-AP) / Vion, Northwestern University - LARVOL DELTA

Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892). (PubMed, Cancer Chemother Pharmacol) - P1 | "Oral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure."

Journal • Metastases • PK/PD data • Cardiovascular • Cervical Cancer • Heart Failure • Hematological Disorders • Hypertension • Leukopenia • Neutropenia • Oncology • Solid Tumor • Vaginal Cancer • CYP1A2

Incorporation of triapine (T) with cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial. (ASCO 2023) - P3 | "The addition of triapine to CRT did not improve OS. Clinical trial information: NCT02466971."

Clinical • IO biomarker • Metastases • P3 data • Cardiovascular • Cervical Cancer • Metabolic Disorders • Oncology • Squamous Cell Carcinoma • Vaginal Cancer

Incorporation of triapine (T) to cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial. (PubMed, Gynecol Oncol) - P3 | "Triapine added to CRT did not improve OS."

Journal • P3 data • Cardiovascular • Cervical Cancer • Metabolic Disorders • Oncology • Solid Tumor • Vaginal Cancer

ETCTN 10388: a first in human phase I trial of triapine and lutetium Lu 177 DOTATATE in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (AACR 2023) - P1 | "The combination of triapine and Lu-177 DOTATATE was safe with preliminary efficacy signals, which will be further evaluated in ETCTN 10558, a randomized phase 2 study that is comparing the effectiveness of triapine and Lu-177 DOTATATE to Lu-177 DOTATATE alone."

P1 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Multi-center NCI-sponsored phase I study of triapine in combination with 177Lu-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs) (ESMO 2025) - P1 | "Triapine (150 mg) is the RP2D. A randomized phase 2 trial (ETCTN 10558) comparing the combination to 177Lu-dotatate monotherapy is currently enrolling at 14 sites across the United States."

Clinical • Combination therapy • P1 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Enhancing triapine treatment: strategies for dose optimization and methemoglobin level mitigation. (PubMed, Cancer Chemother Pharmacol) - "This study provides a quantitative model characterizing the relationship between triapine exposure and methemoglobin concentrations. The developed PK/PD model can be used to optimize the dosing regimen for oral triapine, illustrating how population PK/PD modeling can inform decision-making throughout the triapine drug development lifecycle."

Journal • Endocrine Cancer • Oncology • Solid Tumor

Pharmacokinetics and RP2D analysis from ETCTN 10388: A phase I trial of triapine and lutetium Lu-177 dotatate in well-differentiated somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). (ASCO-GI 2023) - "The RP2D of triapine is 150 mg QD on days 1-14 in combination with Lu-177 DOTATATE on day 1 of every 56-day cycle. Clinical trial information: 04234568."

P1 data • PK/PD data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Systematic screening identified broad-spectrum inhibitors of human-pathogenic Encephalitozoon species and revealed no in vitro activity of nitazoxanide. (PubMed, J Antimicrob Chemother) - "Trimetrexate emerged as the most promising candidate for further anti-microsporidia exploration, whereas nitazoxanide showed no detectable activity under the conditions tested, questioning its role in the treatment of human microsporidiosis."

Journal • Preclinical • CNS Disorders • Infectious Disease • Malaria

Triapine in Combination With Temozolomide for the Treatment of Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=22 | Recruiting | Sponsor: Northwestern University | Trial completion date: May 2030 ➔ Aug 2030 | Trial primary completion date: May 2029 ➔ Jul 2026

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • MGMT

Multi-center Phase 1 study of Triapine in Combination with [177Lu]Lutetium-Dotatate in Patients with Well-Differentiated Neuroendocrine Tumors (ETCTN 10388). (PubMed, Clin Cancer Res) - P1 | "The combination of [¹⁷⁷Lu]lutetium-dotatate (200 mCi) and oral triapine (150 mg D1-14) was well tolerated and demonstrated preliminary activity in patients with well-differentiated GEP-NETs. (NCT04234568)."

Journal • P1 data • Cardiovascular • Gastrointestinal Neuroendocrine Tumor • Hematological Disorders • Leukopenia • Neuroendocrine Tumor • Neutropenia • Oncology • Solid Tumor

A phase II randomized control trial of triapine plus lutetium 177 DOTATATE versus lutetium 177 DOTATATE alone for well-differentiated somatostatin receptor-positive neuroendocrine tumors. (ASCO 2024) - P1 | "Secondary endpoint is to evaluate median PFS. We are also evaluating triapine PK, plasma deoxyribonucleosides, circulating DNA and plasma hPG80, a novel blood based diagnostic biomarker."

Clinical • P2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Distinct Effects of Copper Ionophores on Intracellular Copper and Cell Viability in Wild-Type and CTR1-Deficient SH-SY5Y Cells. (PubMed, ACS Omega) - "In this study, we investigated the effects of selected copper-binding compoundsα-lipoic acid (LA), elesclomol (ES), disulfiram (DSF), thiourea (TU), and triapine (3-AP)on copper uptake and cytotoxicity in SH-SY5Y wild-type (WT) and CTR1-deficient (CTR1-/-) cells. Overall, our results demonstrate that copper ionophores can enhance intracellular copper levels dependently and independently of CTR1, with distinct effects on cell viability. Among the tested compounds, LA and DSF showed a favorable profile by increasing copper levels while maintaining low cytotoxicity, highlighting their potential for modulating cellular copper homeostasis."

Journal • Alzheimer's Disease • CNS Disorders

NRG-GY006: Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers (clinicaltrials.gov) - P3 | N=450 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Jul 2027

Trial completion date • Cervical Adenocarcinoma • Cervical Cancer • Cervical Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Uterine Cancer • Vaginal Cancer

Design and delivery of fluorescent metal-Triapine analogues as theranostic systems: Cellular membranes interactions, confocal imaging and MP Flim cellular mapping (ACS-Fall 2026) - "Correlated imaging studies provide insight into the speciation, stability, and spatial distribution of these complexes in biological systems. Our work establishes fluorescent thiosemicarbazone metal complexes as a versatile platform for probing metal complex behavior and biodistribution using advanced optical imaging techniques, and upon in vivo evaluations these may have potential for drug discovery and for the development of future theranostics."

The role of metals in cancer and the use of metal chelators as a potential treatment strategy. (PubMed, Biometals) - "Thiosemicarbazones, particularly Triapine, have demonstrated anticancer and antimetastatic activity in preclinical models, with clinical trials currently underway to treat tumors...Its efficacy in preclinical models and selective profile support the need for clinical validation, potentially integrating more targeted, safe, and effective oncological therapy. Thus, the aim of this manuscript is to analyze the role of metals in cancer and evaluate the therapeutic potential of metal chelators."

Journal • Review • CNS Disorders • Oncology • Psychiatry

Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • Astrocytoma • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor

Testing the Response to the Anti-cancer Drug, Triapine, in Uterine Cancers Using Markers From the Tissue at the Time of Hysterectomy (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Nov 2026 | Trial primary completion date: Jun 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Gynecology • Oncology • Solid Tumor • Uterine Cancer

A case report of acute carcinoid heart failure during lutetium-177 dotatate-triapine treatment for well-differentiated neuroendocrine tumors. (PubMed, Front Oncol) - P1 | "The patient, a 69-year-old man with gastroenteropancreatic NET with liver metastases and known chronic systolic heart failure (HF), had received octreotide then everolimus therapy prior to enrollment. This case reports the rare complication of an acute exacerbation of carcinoid-associated HF by the [177Lu]lutetium-177 dotatate-triapine combination. The cause of the acute cardiac decompensation could be related to the marked tumor response to treatment and/or contributions of the renoprotective amino acid infusion."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

ETCTN 9892: Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vaginal Cancer (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2026 ➔ Apr 2027

Trial completion date • Cervical Adenocarcinoma • Cervical Cancer • Cervical Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Vaginal Cancer

Ribonucleotide reductase regulatory subunit M2 as a macromolecular target bridging small cell lung cancer progression and SARS-CoV-2 infection. (PubMed, Int J Biol Macromol) - "Molecular docking revealed strong binding of RRM2 to SARS-CoV-2 3CLpro (-21.0 kcal/mol), while the RRM2 inhibitor COH29 exhibited superior affinity compared with Triapine and showed robust stability in molecular dynamics simulation. These findings indicate heightened vulnerability of SCLC patients to adverse COVID-19 outcomes and implicate RRM2 as a potential molecular link between aggressive tumor biology and virus-associated host susceptibility."

Journal • Infectious Disease • Lung Cancer • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • CCNB2 • RRM2 • UBE2C

Combined Inhibition of ATR and Ribonucleotide Reductase Induces Synergistic Antineoplastic Activity in Osteosarcoma Cells. (PubMed, Cancer Rep (Hoboken)) - "Our study demonstrates that combined inhibition of ATR and RNR was effective in osteosarcoma cells. These in vitro findings offer support for investigating in vivo the potential of a combination of ATR and RNR inhibitors as a new treatment strategy for osteosarcoma."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CASP3 • CASP7

Evolution of Thiosemicarbazones: From First- to Second-Generation Metal Chelators and Their Reactive Oxygen Species-Mediated Effects in Melanoma. (PubMed, ChemistryOpen) - "Classical thiosemicarbazones such as Triapine and Dp44mT display multifaceted mechanisms of action, including potent metal ion chelation, inhibition of ribonucleotide reductase (RR), and the induction of oxidative stress through reactive oxygen species (ROS) generation...Preclinical studies demonstrate strong cytotoxicity and some tumor selectivity for these agents, though clinical translation remains limited. The ongoing development of thiosemicarbazone-based therapeutics continues to offer promise for more effective and selective melanoma treatment strategies."

Journal • Review • Melanoma • Oncology • Solid Tumor

Exploring the Role of Novel N (4) Substituted 5,7-Dibromoisatin Thiosemicarbazones in Modulating PTOV1 Activity for Therapeutic Relevance in Breast Cancer. (PubMed, Drug Dev Res) - "Notably, L5 showed superior potency in MCF-7 cells with IC50; 1.16 µM compared to the FDA-approved thiosemicarbazone Triapine with IC50; 4.27 µM, while displaying minimal toxicity toward non-tumorigenic MCF-10a breast epithelial cells with selectivity index > 86.20, consistent with ADMET predictions. Molecular docking and molecular dynamics simulations demonstrated stronger binding affinity and greater complex stability of L5 with PTOV1 compared to the FDA approved drug Lenalidomide, supporting L5 drug likeness and therapeutic potential...L5 enhanced H2AX phosphorylation, suppressed PARP and BCL-XL levels, and increased active caspase-3 driving L5 induced apoptosis. This study identifies L5 as a potent anticancer agent in breast cancer, acting through modulation of the PTOV1-AKT-β-catenin signaling axis, and highlights PTOV1 as a promising therapeutic target."

Journal • Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • AKT1 • BCL2L1 • CASP3 • JUN • MMP2

ETCTN 10388: Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Endocrine Cancer • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Solid Tumor

Mitochondria and Neuromast Tagging With Fluorescent Gallium-Triapine Analogues: In Cellulo MP FLIM and Zebrafish Live Imaging. (PubMed, Adv Sci (Weinh)) - "The combined in vitro and in vivo imaging data provide direct insight into the speciation, stability, and spatial distribution of thiosemicarbazone metal complexes in complex biological systems. This work establishes new fluorescent thiosemicarbazones as versatile platforms for studying metal complex behavior and biodistribution by advanced optical imaging techniques, opening new opportunities for advanced development of new theranostic applications."

Journal • Brain Cancer • Oncology