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

A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine (SNO 2025) - "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."

Breast Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • RRM2

A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine (SNO 2025) - "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."

Breast Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • RRM2

A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine (WFNOS 2025) - "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."

Brain Cancer • Breast Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • RRM2

A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine (WFNOS 2025) - "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."

Brain Cancer • Breast Cancer • Glioblastoma • Solid Tumor • Triple Negative Breast Cancer • RRM2

ETCTN 10558: 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. (NANETS 2025) - P1, P2 | "We are also evaluating triapine PK, plasma deoxyribonucleosides, circulating DNA and plasma hPG80, a novel blood based diagnostic biomarker. NCT05724108 RESULTS N/A CONCLUSIONS N/A"

Clinical • P2 data • 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

Multi-center NCI-sponsored phase 1 study of triapine in combination with 177Lu-dotatate in patients with progressive well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (NANETS 2025) - "The 177Lu-Dotatate (200 mCi) plus triapine (150 mg) regimen has been selected for further evaluation. A randomized phase 2 trial (ETCTN 10558) comparing the combination to standard 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

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) | Initiation date: Mar 2026 ➔ Jul 2025

Trial initiation date • Astrocytoma • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor

Low Catalytic Redox Activity of α-N-Pyridylthiosemicarbazone Iron Complexes Suggests an Indirect ROS Generation Mechanism in Their Biological Activity. (PubMed, Inorg Chem) - "In this respect, the catalytic activity of the Fe complexes of two PTSCs, Triapine (3AP) and Dp44mT, with the two most abundant reducing agents, ascorbate and glutathione, was evaluated under aerobic conditions...Thus, Fe-PTSC and Fe-PTSC2 are unlikely to drive ROS production through a direct mechanism. Instead, an indirect mechanism or a site-specific ROS production appears to be more plausible."

Journal • Oncology • CAT

Regulation of neurogenesis and neuronal migration by Rrm2 and Timp3 following seizures. (PubMed, Neurobiol Dis) - "Using a pilocarpine-induced mouse model of temporal lobe epilepsy and chemogenetic silencing of abGCs via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we previously demonstrated that abGC inhibition reduces both ectopic migration and seizure susceptibility...To assess their functional roles, we pharmacologically inhibited Rrm2 with Triapine (3-AP) and Timp3 with the LXR agonist T0901317 (T09)...These findings highlight distinct roles of Rrm2 and Timp3 in hippocampal plasticity following seizures. Together, these data identify new molecular targets for modulating aberrant neurogenesis in epilepsy."

Journal • CNS Disorders • Epilepsy • RRM2 • TIMP3

The anticancer thiosemicarbazone triapine exerts immune-enhancing activities via immunogenic cell death induction and FAS upregulation. (PubMed, Exp Hematol Oncol) - "The anticancer thiosemicarbazone Triapine is currently in a phase III clinical trial in combination with radiation therapy and cisplatin. This, in turn, rendered cancer cells more susceptible to FASL (predominantly expressed by lymphoid immune cells)-induced caspase 8-mediated apoptosis. Consequently, our study is the first to unveil the significant role of the (adaptive) immune system in the anticancer activity of Triapine, positioning it as a promising partner for combination with immunotherapy and other immunogenic agents."

Journal • Immunology • Oncology • CALR • CASP8 • FASLG • HMGB1

Disulfide-based 2-pyridyl-hydrazone prochelators induce iron deprivation and oxidative stress in ovarian cancer cells. (PubMed, J Biol Inorg Chem) - "We report the synthesis and biological evaluation of disulfide-based prochelators featuring a 2-pyridyl-hydrazone motif and resulting in a tridentate (S,N,N) donor set as found in several antiproliferative chelators (e.g., Triapine, Dp44mT, DpC, COTI-2). Accordingly, the preformed iron complex FePH3 also leads to apoptosis and iron dysregulation, and its toxicity is enhanced when the antioxidant capacity of the cells is impaired. The incorporation of the 2-pyridyl-hydrazone motif in disulfide-based prochelators therefore combines iron sequestration with pro-oxidant effects that could enhance the pharmacological profile of this chelation approach for cancer applications."

Journal • Oncology • Ovarian Cancer • Solid Tumor • TFRC

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: Oct 2025 ➔ Jun 2026

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

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 | Suspended | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

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

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) | Initiation date: Jun 2025 ➔ Mar 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Astrocytoma • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • 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 2025 ➔ Apr 2026

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

RRM2-driven dNTP biosynthesis: a therapeutic vulnerability in temozolomide-resistant glioblastoma (AACR 2025) - "Recognizing the limitations of first-generation RNR inhibitors, we explored the second-generation inhibitor Triapine (3-AP). These findings underscore the potential of targeting RRM2-mediated dNTP biosynthesis to overcome chemoresistance in GBM. We are conducting a Phase 1/1b clinical trial to assess the safety, toxicity, and maximum tolerated dose (MTD) of combining 3-AP with TMZ in recurrent GBM patients."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • RRM1 • RRM2 • RRM2B

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

Testing the Effectiveness of an Anti-cancer Drug, Triapine, When Used With Targeted Radiation-based Treatment (Lutetium Lu 177 Dotatate), Compared to Lutetium Lu 177 Dotatate Alone for Metastatic Neuroendocrine Tumors (clinicaltrials.gov) - P2 | N=94 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Sep 2025 | Trial primary completion date: Mar 2025 ➔ Sep 2025

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

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=33 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Sep 2024

Trial completion date • Trial primary completion date • Endocrine Cancer • Neuroendocrine Tumor • 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 | Suspended | Sponsor: National Cancer Institute (NCI) | Trial completion date: Feb 2025 ➔ Jun 2025 | Trial primary completion date: Feb 2025 ➔ Jun 2025

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

Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1 trial • Astrocytoma • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor

Study on the effects and mechanism of RRM2 on three gynecological malignancies. (PubMed, Cell Signal) - "The potential oncogenic effects of RRM2 in gynecologic tumor cell lines were further demonstrated using the RRM2 inhibitor Triapine (3-AP). These pro-tumorigenic effects may then be mediated through the involvement of RRM2 in the p53 and Akt/mTOR signaling pathways, altering the expression of p53 and Akt/mTOR. Thus, RRM2 is potentially a candidate gene for the unified diagnosis of cervical, endometrial, and ovarian cancers."

Journal • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Women's Health • AKT1 • RRM2

Combined inhibition of ribonucleotide reductase and WEE1 induces synergistic anticancer activity in Ewing's sarcoma cells. (PubMed, BMC Cancer) - "Our findings show that combined inhibition of RNR and WEE1 was effective against Ewing's sarcoma in vitro. They thus provide a rationale for the evaluation of the potential of combined targeting of RNR and WEE1 in Ewing's sarcoma in vivo."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • CASP3 • CASP7 • CHEK1

DefNEtTrp: An Iron Dual Chelator Approach for Anticancer Application. (PubMed, JACS Au) - "Two important chelators, deferasirox (Def) and triapine (Trp), attack the intracellular supply of iron (Fe) and inhibit Fe-dependent pathways responsible for cellular proliferation and metastasis...Its cytotoxicity (IC50 0.77 ± 0.06 μM) is superior to that of unconjugated Def and Trp ligands (IC50 2.6 ± 0.15 μM and 1.1 ± 0.04 μM, respectively) in single-compound and combination treatments and is selective toward cancer cells. The cell death mechanism of the dual chelator is assessed in the context of intracellular labile Fe binding and was found to induce both apoptosis and ferroptosis."

Journal • Oncology