Triapine (3-AP) / Vion, Northwestern University 
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 194 Diseases   7 Trials   7 Trials   234 News 


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  • ||||||||||  COTI-2 / Cotinga Pharma
    Journal:  Thiosemicarbazone Derivatives Developed to Overcome COTI-2 Resistance. (Pubmed Central) -  Sep 25, 2022   
    These data revealed that, besides zinc, also iron and copper ions need to be considered to play a role in the mode of action and resistance development of these thiosemicarbazones. Moreover, we identified COTI-NMe as an interesting new drug candidate with improved anticancer activity and resistance profile.
  • ||||||||||  Triapine (3-AP) / Vion
    Design, synthesis, and evaluation of a novel bifunctional iron chelator as a potential inhibitor of ribonucleotide reductase (W179a (McCormick Place Convention Center)) -  Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_13807;    
    In an effort to evolve the Ti(deferasirox)2 compound into a specific inhibitor of RNR we have designed and synthesized a novel ligand based on the conjugation of the Fe(II)/(III) chelator, triapine, with deferasirox because triapine has the capacity to bind at the diiron site of RNR...We also evaluated the cytotoxicity/antiproliferative activity of the ligand against the leukemia Jurkat cell line where it displays a superior cytotoxic behavior versus the combination of the separate molecules. This work serves to improve the cancer cell selectivity of our Ti(IV) compound and the specificity of its activity.
  • ||||||||||  Triapine (3-AP) / Vion
    Titanium and iron chelators: A transmetallative approach to human ribonucleotide reductase inhibition (W179a (McCormick Place Convention Center)) -  Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_13805;    
    Literature suggests that the tridentate iron chelator triapine, complexed to metals such as Fe(III), Ga(III), Cu(II) and Zn(II), has been able to reduce tyrosyl radical in RNR significantly...Furthermore, the impact of iron chelators on RNR’s dimetallic center has been evaluated. The findings of this research serve as optimization for a transmetallative approach to RNR inhibition.
  • ||||||||||  Triapine (3-AP) / Vion
    Preclinical, Journal:  Co-administration of Inulin and Iron Fortificants improves Iron Deficiency Biomarkers in Female Sprague Dawley Rats. (Pubmed Central) -  Jul 20, 2022   
    Treatment groups were made iron deficient by feeding them with triapine, an iron binder for two weeks...Also, mean values of total iron-binding capacity and serum transferrin showed a steady decline over a period of three months indicating that iron stores were being improved. It was concluded that co-administration of inulin and iron fortificants helped improve iron deficiency biomarkers in female Sprague Dawley rats.
  • ||||||||||  Triapine (3-AP) / Vion
    Targeting Plasticity-driven Adaptation to Overcome Chemoresistance in GBM (Zeremoniensaal) -  Jul 19, 2022 - Abstract #EANO2022EANO_233;    
    In addition, treatment with RRM2-inhibitor, 3-AP Triapine, enhances the efficacy of TMZ therapy in PDX models. We present a novel understanding of chemoresistance through critical RRM2-mediated nucleotide production.
  • ||||||||||  Triapine (3-AP) / Vion
    Review, Journal:  Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present. (Pubmed Central) -  Jul 2, 2022   
    In this review, we discuss the mechanisms and clinical applications of classic nucleoside analog inhibitors of hRRM1 (large catalytic subunit), including gemcitabine and clofarabine, as well as inhibitors of the hRRM2 (free radical housing small subunit), including triapine and hydroxyurea. Additionally, we discuss novel approaches to targeting RR and the discovery of new classes of hRR inhibitors.
  • ||||||||||  Triapine (3-AP) / Vion, adavosertib (AZD1775) / AstraZeneca
    Ribonucleotide reductase M2 subunit switching in hepatoblastoma drug resistance and relapse (Section 23) -  Mar 9, 2022 - Abstract #AACR2022AACR_5913;    
    Our data suggest that RRM2 supports HB growth while its switching to RRM2B is critical to tumor cell survival under drug treatment. When tumor relapses, there is a reversed subunit switch from RRM2B to RRM2 to supports the recurrent growth of the tumor, which can serve as a potential therapeutic target in preventing HB relapse.
  • ||||||||||  Triapine (3-AP) / Vion
    Review, Journal:  Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine. (Pubmed Central) -  Mar 8, 2022   
    In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones), e.g., deferiprone, anthraquinones, e.g., doxorubicin and thiosemicarbazones, e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential clinical applications, including anticancer activity. Furthermore, the redox properties of these three classes of chelators were compared to those of the iron chelating drugs and also to vitamin C, with an emphasis on their potential clinical interactions and future clinical application prospects in cancer, neurodegenerative and other diseases.
  • ||||||||||  Triapine (3-AP) / Vion, COTI-2 / Cotinga Pharma
    Journal:  Liposomal formulations of anticancer copper(II) thiosemicarbazone complexes. (Pubmed Central) -  Feb 22, 2022   
    Also in vivo distinctly higher copper plasma levels and a continuous release could be observed for the liposomal formulation compared to free Cu-triapine. Taken together, the here presented nanoformulation of Cu-triapine is an important step further to increase the plasma half-life time and tumor targeting properties of anticancer thiosemicarbazones.
  • ||||||||||  Triapine (3-AP) / Vion
    Coordination of a novel iron-chelating conjugate, Deferasirox NEt-Triapine, to Titanium(IV) to develop a three-pronged anticancer drug (Room 7A (San Diego Convention Center)) -  Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_385;    
    In this paper, we describe the synthesis and characterization of DefNEtTrp and its coordination to Ti(IV), as well as assess its ability to produce an inhibitory effect on RNR. Through UV-Vis spectroscopy, MALDI-TOF/TOF, and cyclic voltammetry analyses, we determined that the novel complex, Ti(DefNEtTrp)2, would be able to inhibit RNR by: attacking the intracellular supply of iron and ribonucleotides, as well as quenching the enzyme’s activating tyrosyl radical.
  • ||||||||||  Triapine (3-AP) / Vion
    Biomarker, Journal:  Translational evidence for RRM2 as a prognostic biomarker and therapeutic target in Ewing sarcoma. (Pubmed Central) -  Jan 27, 2022   
    Through UV-Vis spectroscopy, MALDI-TOF/TOF, and cyclic voltammetry analyses, we determined that the novel complex, Ti(DefNEtTrp)2, would be able to inhibit RNR by: attacking the intracellular supply of iron and ribonucleotides, as well as quenching the enzyme’s activating tyrosyl radical. No abstract available
  • ||||||||||  Triapine (3-AP) / Vion, Lynparza (olaparib) / Merck (MSD), AstraZeneca
    Journal, BRCA Biomarker, PARP Biomarker:  In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer. (Pubmed Central) -  Nov 6, 2021   
    Furthermore, we demonstrated that the combination of DB4 and olaparib deterred the progression of BRCA-wild type EOC xenografts and significantly prolonged the survival time of tumor-bearing mice. Herein we report the discovery of a putative small molecule inhibitor of RNR and HR repair for combination with PARP inhibitors to treat PARP inhibitor-resistant and HR repair-proficient EOC.
  • ||||||||||  Triapine (3-AP) / Vion, Desferal (deferoxamine) / Kermanshah University of Medical Sciences, Novartis
    Review, Journal:  Iron chelators in cancer therapy. (Pubmed Central) -  Sep 29, 2021   
    This review examines and discusses the various iron chelators that have been trialled for cancer therapy including both preclinical and clinical studies. The successes and shortcomings of each of the chelators and their use in combination therapies are highlighted and future potential in the cancer therapy world is considered.
  • ||||||||||  Triapine (3-AP) / Vion
    Journal:  Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes: Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity. (Pubmed Central) -  Sep 22, 2021   
    The prepared copper(II) complexes and their metal-free ligands revealed antiproliferative activity against highly resistant cancer cell lines, including triple negative breast cancer cells MDA-MB-231, sensitive COLO-205 and multidrug resistant COLO-320 colorectal adenocarcinoma cell lines, as well as in healthy human lung fibroblasts MRC-5 and compared to those for triapine and doxorubicin. In addition, their ability to reduce the tyrosyl radical in mouse R2 protein of ribonucleotide reductase has been ascertained by EPR spectroscopy and the results were compared with those for triapine.
  • ||||||||||  Triapine (3-AP) / Vion
    Journal:  Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells. (Pubmed Central) -  Sep 15, 2021   
    While the free ligands HL and HL were devoid of antiproliferative activity, their respective metal complexes showed remarkable antiproliferative activity in a micromolar concentration range. The activity was not related to the inhibition of ribonucleotide reductase (RNR) R2 protein, but rather to cancer cell homeostasis disturbance-leading to the disruption of cancer cell signalling.
  • ||||||||||  Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
    Journal, PARP Biomarker:  Development and validation of an LC-MS/MS generic assay platform for small molecule drug bioanalysis. (Pubmed Central) -  Jul 23, 2021   
    HL and 1 in the presence of 1,4-dithiothreitol are as potent inhibitors of mR2 ribonucleotide reductase as triapine. The generic approach has become a useful tool to further define the pharmacology of drugs studied in our laboratory and may be utilized as described, or as starting point to develop drug-specific assays with more extensive performance characterization.
  • ||||||||||  Triapine (3-AP) / Vion
    Journal:  Binding Models of Copper(II) Thiosemicarbazone Complexes with Human Serum Albumin: A Speciation Study. (Pubmed Central) -  Jun 24, 2021   
    The partially negatively charged tetrapeptide binds stronger to the positively charged Triapine complex in comparison to the neutral STSC complex, while the opposite trend was observed for HSA, which demonstrates the limitations of the use of simple ligands to model the protein binding. The studied TSC complexes are able to bind to HSA in a fast process, and the conditional constants suggest that their binding strength is only weak-to-moderate.
  • ||||||||||  Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
    Clinical, Review, Journal, IO biomarker:  Novel therapeutics for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors. (Pubmed Central) -  Jun 8, 2021   
    And though single-agent immune checkpoint inhibitors have not demonstrated significant anti-tumor activity in patients with GEP NETs, outside of certain biomarker selected subsets, somatostatin receptor-directed chimeric antigen receptor (CAR) T cells and vaccines such as SurVaxM, which targets survivin, represent two means through which NET-directed immunity may be modulated. The potential of these agents, if clinically realized, will likely improve outcomes for patients with well-differentiated GEP NETs.
  • ||||||||||  Triapine (3-AP) / Vion, COTI-2 / Cotinga Pharma
    Journal:  Anticancer thiosemicarbazones: chemical properties, interaction with iron metabolism, and resistance development. (Pubmed Central) -  Jun 18, 2020   
    In contrast, they should be considered as iron-interacting drugs influencing diverse biological pathways with a complex and multi-facetted mode of action. Consequently, in addition to the discussion of physicochemical properties (e.g. complex stability, redox activity), this review contains an overview on the diversity of cellular thiosemicarbazone targets and drug resistance mechanisms.