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  • ||||||||||  BOLD-100 / Bold Therap
    Preclinical, Journal:  Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103. (Pubmed Central) -  Mar 27, 2024   
    Our results indicate that the higher injected dose (30 mg kg-1) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [103Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [97Ru]BOLD-100.
  • ||||||||||  ceralasertib (AZD6738) / AstraZeneca, BOLD-100 / Bold Therap
    Co-downregulation of GRP78 and ATR enhances apoptosis in pancreatic ductal adenocarcinoma (Section 16) -  Mar 5, 2024 - Abstract #AACR2024AACR_2892;    
    GRP78 could serve as one of the potential therapeutic targets in PDAC. The combination of BOLD-100 and AZD6738 demonstrates a synergistic effect suggesting GRP78/ATR dual targeting as a promising therapeutic option for patients with PDAC.
  • ||||||||||  BOLD-100 / Bold Therap
    Preclinical, Journal:  Synthesis and Preclinical Evaluation of Radiolabeled [Ru]BOLD-100. (Pubmed Central) -  Nov 25, 2023   
    The cytotoxicity of the compounds was determined in two colon carcinoma cell lines (HCT116 and CT26) and biodistribution studies were performed in Balb/c mice bearing CT26 allografts over a time period of 72 h post injection (p.i.). We report herein preclinical cytotoxicity and pharmacokinetic data for BOLD-100, which were found to be identical to those of its radiolabeled analog [Ru]BOLD-100.
  • ||||||||||  BOLD-100 / Bold Therap
    Enrollment closed, Combination therapy, Metastases:  BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov) -  Sep 18, 2023   
    P1b/2a,  N=117, Active, not recruiting, 
    Identification of the lipid metabolism as driver of acquired BOLD-100 resistance opens novel strategies to tackle therapy failure. Recruiting --> Active, not recruiting
  • ||||||||||  BOLD-100 / Bold Therap
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov) -  Feb 10, 2023   
    P1b/2a,  N=100, Recruiting, 
    Analysis of additional patient samples from the Phase 2 trial is ongoing. Trial completion date: Dec 2023 --> Sep 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
  • ||||||||||  BOLD-100 / Bold Therap
    Phase classification, Trial completion date, Combination therapy, Metastases:  BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov) -  Nov 18, 2022   
    P1b/2a,  N=100, Recruiting, 
    In summary, targeting O-glycosylation rep- resents a potential new approach to circumvent BOLD-100 resistance. Phase classification: P1b --> P1b/2a | Trial completion date: Jan 2023 --> Dec 2023
  • ||||||||||  BOLD-100 / Bold Therap
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov) -  Jul 28, 2022   
    P1b,  N=80, Recruiting, 
    Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM. Trial completion date: Mar 2022 --> Jan 2023 | Trial primary completion date: Dec 2021 --> Dec 2022
  • ||||||||||  BOLD-100 / Intezyne, Bold Therap
    Utilization of cancer cell line screening and bioinformatic analyses to identify optimal developmental pathways for the novel anticancer agent BOLD-100 (E-Poster Website) -  Mar 9, 2022 - Abstract #AACR2022AACR_6948;    
    Utilizing bladder cancer as a case study, subsequent combination testing of BOLD-100 in combination with fluorouracil or cisplatin demonstrated that BOLD-100 enhanced cell death across different bladder cancer cell lines through synergistic interactions with these standard-of-care agents...Collectively, BOLD-100 showed a unique sensitivity profile across a panel of over 300 cancer cell lines, identifying multiple potential indications for future development. Subsequent investigations into several cancer types of interest and drug combinations are ongoing.
  • ||||||||||  cisplatin / Generic mfg.
    Review, Journal:  Ruthenium(ii)-arene complexes as anti-metastatic agents, and related techniques. (Pubmed Central) -  Mar 1, 2022   
    With the discovery of cisplatin, a vast area of applications of metallodrugs in cancer treatment was opened but due to the side effects caused by the cisplatin complexes, researchers began to look for alternatives with similar anticancer properties but fewer side effects...NAMI-A, KP1019, KP1339, and TLD1433, have entered clinical trials...Herein, we provide information and probable mechanistic pathways for ruthenium(ii)-arene complexes that have been studied, so far, for their anti-metastatic activities. Also, we discuss the techniques and their significance for determining the anti-metastatic effects of the complexes.
  • ||||||||||  BOLD-100 / Intezyne, Bold Therap
    Review, Journal:  Ruthenium Complexes: An Alternative to Platinum Drugs in Colorectal Cancer Treatment. (Pubmed Central) -  Aug 29, 2021   
    Ru-nanoformulations improve drug efficacy, targeted drug delivery, immune activation, and biocompatibility, and therefore may be capable of overcoming some of the existing chemotherapeutic limitations. Among the potential Ru-based compounds, only Ru (III)-based drug NKP-1339 has undergone phase-Ib clinical trials in CRC treatment.
  • ||||||||||  BOLD-100 / Intezyne, Bold Therap
    Journal:  Thermodynamic Genome-Scale Metabolic Modeling of Metallodrug Resistance in Colorectal Cancer. (Pubmed Central) -  Aug 28, 2021   
    Among the potential Ru-based compounds, only Ru (III)-based drug NKP-1339 has undergone phase-Ib clinical trials in CRC treatment. Here, we elucidate the key importance of normalization steps in the interpretation of metabolomics data, allowing us to uncover drug-specific metabolic reprogramming during acquired metal-drug resistance.
  • ||||||||||  cisplatin / Generic mfg.
    Review, Journal:  Emerging Molecular Receptors for the Specific-Target Delivery of Ruthenium and Gold Complexes into Cancer Cells. (Pubmed Central) -  Jul 9, 2021   
    Cisplatin and derivatives are highly effective in the treatment of a wide range of cancer types; however, these metallodrugs display low selectivity, leading to severe side effects...This scenario triggered the study of other transition metals with innovative pharmacological profiles as alternatives to platinum, ruthenium- (e.g., KP1339 and NAMI-A) and gold-based (e.g., Auranofin) complexes being among the most advanced in terms of clinical evaluation...Finally, we describe some complexes aimed at recognizing cell organelles or compartments, mitochondria being the most explored. The few complexes addressing targeted gene therapy are also presented and discussed.
  • ||||||||||  BOLD-100 / Intezyne, Bold Therap
    Review, Journal:  Ruthenium Complexes in the Fight against Pathogenic Microorganisms. An Extensive Review. (Pubmed Central) -  Jul 4, 2021   
    Some aspects regarding the relationship between their chemical structure and mechanism of action, cellular localization, and/or metabolism of the ruthenium complexes in bacterial and eukaryotic cells are discussed as well. Regarding the antiviral activity, in light of current events related to the Covid-19 pandemic, the Ru (II/III) compounds used against SARS-CoV-2 (e.g., BOLD-100) are also reviewed herein.
  • ||||||||||  cisplatin / Generic mfg.
    Preclinical, Journal:  Rhenium-based complexes and in vivo testing: A brief history. (Pubmed Central) -  Jun 30, 2021   
    The success of metal-based anticancer therapeutics in the treatment of cancer is best exemplified by cisplatin...This has led to investigations of other metal-based drug candidates such as auranofin, a gold-based drug candidate as well as ruthenium-based candidates, NAMI-A, NKP-1339 and TLD-1433...Another class of complexes under study are rhenium-based; such complexes have undergone extensive in vitro testing but only seven have displayed antitumor in vivo activity which is a necessary step before entering clinical trials. This present review will document, chronologically, the rhenium-based drug candidates that have undergone in vivo testing and the outlook for such complexes.
  • ||||||||||  BOLD-100 / Bold Therap
    Enrollment open, Combination therapy, Metastases:  BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov) -  Oct 7, 2020   
    P1b,  N=80, Recruiting, 
    The study was opened for enrollment in August 2020; approximately 25-30 patients will be screened to achieve up to 20 patients in Part A and up to 80 patients will be enrolled in Part B with a maximum of 25 patients per arm. Not yet recruiting --> Recruiting
  • ||||||||||  IT-139 / Intezyne, Bold Therap
    Preclinical, Journal, Immunogenic cell death:  First-in-class ruthenium anticancer drug (KP1339/IT-139) induces an immunogenic cell death signature in colorectal spheroids in vitro. (Pubmed Central) -  Jun 5, 2020   
    As some metal-based chemotherapeutics such as oxaliplatin are able to induce ICD, we investigate whether KP1339 could also trigger induction of the ICD signature. For this, we employ a three-dimensional colon cancer spheroid model and show for the first time that the treatment with KP1339, a ruthenium-based complex, triggers an ICD signature hallmarked by phosphorylation of PERK and eIF2α, exposure of calreticulin on the cell membrane, release of high mobility group box 1 and secretion of ATP.
  • ||||||||||  IT-139 / Intezyne, Bold Therap
    Lipid metabolism as target and modulator of KP1339 anticancer activity (Virtual Meeting II: E-Posters) -  May 16, 2020 - Abstract #AACRII2020AACR-II_1022;    
    We suggest the development of rational combination schemes between lipid metabolism modulators, like etomoxir, and KP1339 for enhanced activity and resistance prevention. The respective preclinical in vivo experiments are currently initiated.
  • ||||||||||  IT-139 / Intezyne
    Clinical, Review, Journal:  NAMI-A and KP1019/1339, Two Iconic Ruthenium Anticancer Drug Candidates Face-to-Face: A Case Story in Medicinal Inorganic Chemistry. (Pubmed Central) -  Nov 23, 2019   
    NAMI-A ((ImH)[trans-RuCl(dmso-S)(Im)], Im = imidazole) and KP1019/1339 (KP1019 = (IndH)[trans-RuCl(Ind)], Ind = indazole; KP1339 = Na[trans-RuCl(Ind)]) are two structurally related ruthenium(III) coordination compounds that have attracted a lot of attention in the medicinal inorganic chemistry scientific community as promising anticancer drug candidates...Despite their evident structural relatedness, deeply distinct biological and pharmacological profiles do emerge. Overall, these two iconic ruthenium complexes form an exemplary and unique case in the field of medicinal inorganic chemistry.
  • ||||||||||  IT-139 / Intezyne
    Journal:  Ru(II) Compounds: Next-generation anticancer metallotherapeutics? (Pubmed Central) -  Jun 26, 2019   
    ...The development of antineoplastic ruthenium therapeutics is of particular interest because ruthenium containing complexes NAMI-A, KP1019, and KP1339 entered clinical trials and DW1/2 is in preclinical levels...A new photodynamic therapy based Ru(II) therapeutic, TLD-1433, has also entered clinical trials. Ru(II)-based compounds also can be photosensitizers for photodynamic therapy, which has proven to be an effective new, alternative, and noninvasive oncotherapy modality.
  • ||||||||||  IT-139 / Intezyne
    Journal:  Reactivity and Transformation of Antimetastatic and Cytotoxic Rhodium(III)-Dimethyl Sulfoxide Complexes in Biological Fluids: An XAS Speciation Study. (Pubmed Central) -  May 2, 2019   
    The reaction of A1 with chemically degraded collagen gel was postulated to be a key reason for its antimetastatic activity. Analyses of the XAS of Rh-treated bulk cells were consistent with structure-reactivity relationships in which the more reactive A1 was predominantly antimetastatic and the less reactive A2 was predominantly cytotoxic, showing relationships parallel to typical Ru(III) anticancer agents, i.e., NAMI-A ([ImH] trans-[RuCl( S-dmso)( N-imidazole)], ImH = imidazolium cation) and KP1019/NKP1339 (KP1019, [IndH] trans-[RuCl(N-indazole)], IndH = indazolium cation; NKP1339, sodium trans-[RuCl(N-indazole)]), respectively.
  • ||||||||||  BOLD-100 / Bold Therap, Intezyne
    Trial primary completion date, Metastases:  Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors (clinicaltrials.gov) -  Apr 7, 2017   
    P1,  N=46, Completed, 
    Analyses of the XAS of Rh-treated bulk cells were consistent with structure-reactivity relationships in which the more reactive A1 was predominantly antimetastatic and the less reactive A2 was predominantly cytotoxic, showing relationships parallel to typical Ru(III) anticancer agents, i.e., NAMI-A ([ImH] trans-[RuCl( S-dmso)( N-imidazole)], ImH = imidazolium cation) and KP1019/NKP1339 (KP1019, [IndH] trans-[RuCl(N-indazole)], IndH = indazolium cation; NKP1339, sodium trans-[RuCl(N-indazole)]), respectively. Trial primary completion date: Dec 2012 --> May 2012
  • ||||||||||  BOLD-100 / Bold Therap, Intezyne
    Enrollment closed, Metastases:  Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors (clinicaltrials.gov) -  Dec 30, 2012   
    P1,  N=50, Active, not recruiting, 
    Trial primary completion date: Dec 2012 --> May 2012 Recruiting --> Active, not recruiting