Last update 04 Nov 2024
Dexrazoxane Hydrochloride
Last update 04 Nov 2024
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms dexrazoxane, Topotect, Totect + [13] |
Target |
Mechanism Top II inhibitors(Topoisomerase II inhibitors) |
Therapeutic Areas |
Inactive Indication |
Originator Organization |
Inactive Organization |
Drug Highest PhaseApproved |
First Approval Date US (26 May 1995), |
RegulationOrphan Drug (US), Orphan Drug (AU), Accelerated Approval (US) |
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Structure
Molecular FormulaC11H17ClN4O4 |
InChIKeyBIFMNMPSIYHKDN-FJXQXJEOSA-N |
CAS Registry149003-01-0 |
Related
52
Clinical Trials associated with Dexrazoxane HydrochlorideProspective Treatment of Types I, II and III Pleuropulmonary Blastoma (PPB)
ANTICIPATE: Prevention of ANThracycline-Induced Cardiac Dysfunction by Dexrazoxane In PATients With diffusE Large B-cell Lymphoma: a Phase III National Multicenter Prospective Randomized Open-label Trial
A Phase II, Single Arm, Open Label, Study on the Safety, Efficacy, Pharmacokinetics & Pharmacodynamics of Quizartinib + Chemotherapy and as Single-agent After High Dose Therapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients
100 Clinical Results associated with Dexrazoxane Hydrochloride
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100 Translational Medicine associated with Dexrazoxane Hydrochloride
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100 Patents (Medical) associated with Dexrazoxane Hydrochloride
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841
Literatures (Medical) associated with Dexrazoxane Hydrochloride01 Dec 2024TOXICOLOGY
Knock-down of FOXO3, GATA2, NFE2L2 and AHR promotes doxorubicin-induced cardiotoxicity in human cardiomyocytes
Article
Author: Asensio, J Ochoteco ; van den Beucken, T ; Caiment, F ; Faber, J G
Recent advances in cancer therapy have substantially increased survival rates among patients, yet the prolonged effect of current treatment regimens with anthracyclines (ACs) often include severe long-term complications, notably in the form of anthracycline-induced cardiotoxicity (AIC). Despite known associations between AC treatment and AIC, a comprehensive understanding of the underlying molecular pathways remains elusive. This gap is highlighted by the scarcity of reliable therapeutic interventions, with dexrazoxane being the sole FDA-approved drug to mitigate AIC risks. This study aims at elucidating the transcriptional response of human cardiomyocytes (hCMs) to AC exposure by analyzing a previously generated RNA-sequencing dataset of cardiac spheroids subjected to clinically relevant doses of ACs. The analysis revealed a robust transcriptional response identified across various time points. We aimed at identifying important transcription factors (TFs) mediating AIC by employing predictive algorithms to highlight key TFs for further experimental validation. Using shRNA constructs, we further assessed the impact of these TFs on hCM response to doxorubicin (DOX) and revealed that these TFs had a notable impact on hCM survival upon DOX exposure. TFs FOXO3, GATA2, AHR and NFE2L2 were further investigated for their role in AIC including cell viability, DOX uptake, DNA damage repair and induction of apoptosis through Cleaved-Caspase 3. Our study demonstrated that eliminating FOXO3 and GATA2 made hCMs more vulnerable to DOX and the lack of GATA2, NFE2L2 and AHR led to significantly higher intracellular levels of DOX. Additionally, FOXO3 played a role in the repair of hCM DNA damage as we observed markedly enhanced levels of CDKN1A. We also noted significant increases in DNA damage through COMET-assays when FOXO3, GATA2, NFE2L2 and AHR were absent. Furthermore, we investigated the clinical relevance by comparing our results with those from a study based on hiPSC-CMs derived from patients with doxorubicin-induced cardiotoxicity, identifying overlapping TFs and their regulatory roles in critical cellular processes like the cell cycle and DNA repair. This approach not only advances the understanding of the molecular mechanisms behind AIC but also opens possible windows for new therapeutic approaches to mitigate the negative side-effects from patient AC treatment.
10 Sep 2024MOLECULES
Rational Design, Synthesis, Molecular Docking, and Biological Evaluations of New Phenylpiperazine Derivatives of 1,2-Benzothiazine as Potential Anticancer Agents.
Article
Author: Janek, Tomasz ; Zaręba, Natalia ; Szczęśniak-Sięga, Berenika M ; Czyżnikowska, Żaneta ; Kepinska, Marta
The aim of this study was to obtain new, safe, and effective compounds with anticancer activity since cancer is still the leading cause of mortality worldwide. The rational design of new compounds was based on the introduction of differentially substituted phenylpiperazines into the 1,2-benzothiazine scaffold as a reference for the structures of recent topoisomerase II (Topo II) inhibitors such as dexrazoxane and XK-469. The newly designed group of 1,2-benzothiazine derivatives was synthesized and tested on healthy (MCF10A) and cancer (MCF7) cell lines, alone and in combination with doxorubicin (DOX). In addition, molecular docking studies were performed both to the DNA-Topo II complex and to the minor groove of DNA. Most of the tested compounds showed cytotoxic activity comparable to doxorubicin, a well-known anticancer drug. The compound BS230 (3-(4-chlorobenzoyl)-2-{2-[4-(3,4-dichlorophenyl)-1-piperazinyl]-2-oxoethyl}-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide) showed the best antitumor activity with lower cytotoxicity towards healthy cells and at the same time stronger cytotoxicity towards cancer cells than DOX. Moreover, molecular docking studies showed that BS230 has the ability to bind to both the DNA-Topo II complex and the minor groove of DNA. Binding of the minor groove to DNA was also proven by fluorescence spectroscopy.
01 Sep 2024Journal of Zhejiang University-SCIENCE B
Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
Article
Author: Zhang, Mengyu ; Zou, Hai ; Zhu, Quanfeng ; Luo, Ting ; Shou, Huafeng ; Yang, Xue ; Chen, Xiaoyi ; Mou, Xiaozhou ; Chen, Zhenglin
Doxorubicin (DOX) is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors; however, its clinical application is limited by significant cardiotoxicity. Cynaroside (Cyn) is a flavonoid glycoside distributed in honeysuckle, with confirmed potential biological functions in regulating inflammation, pyroptosis, and oxidative stress. Herein, the effects of Cyn were evaluated in a DOX-induced cardiotoxicity (DIC) mouse model, which was established by intraperitoneal injections of DOX (5 mg/kg) once a week for three weeks. The mice in the treatment group received dexrazoxane, MCC950, and Cyn every two days. Blood biochemistry, histopathology, immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment. The results demonstrated the significant benefits of Cyn treatment in mitigating DIC; it could effectively alleviate oxidative stress to a certain extent, maintain the equilibrium of cell apoptosis, and enhance the cardiac function of mice. These effects were realized via regulating the transcription levels of pyroptosis-related genes, such as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, and gasdermin D (GSDMD). Mechanistically, for DOX-induced myocardial injury, Cyn could significantly modulate the expression of pivotal genes, including adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), sirtuin 3 (SIRT3), and nuclear factor erythroid 2-related factor 2 (Nrf2). We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway, which plays a central role in preventing DOX-induced cardiomyocyte injury. In conclusion, the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.
3
News (Medical) associated with Dexrazoxane Hydrochloride11 Aug 2023
AcquisitionLicense out/in
10 Aug 2023
AcquisitionRadiation Therapy
03 Jan 2012
100 Deals associated with Dexrazoxane Hydrochloride
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External Link
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D07807 | Dexrazoxane Hydrochloride |
R&D Status
Approved
10 top approved records. to view more data
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| Indication | Country/Location | Organization | Date |
|---|---|---|---|
| Extravasation of Diagnostic and Therapeutic Materials | EU | 27 Jul 2006 | |
| Extravasation of Diagnostic and Therapeutic Materials | IS | 27 Jul 2006 | |
| Extravasation of Diagnostic and Therapeutic Materials | LI | 27 Jul 2006 | |
| Extravasation of Diagnostic and Therapeutic Materials | NO | 27 Jul 2006 | |
| Cytoprotective Agent | CN | 29 May 2006 | |
| Cardiomyopathies | US | 26 May 1995 | |
| Metastatic breast cancer | US | 26 May 1995 |
Developing
10 top R&D records. to view more data
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| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Hemorrhage | Phase 3 | DK | 01 Apr 2002 | |
| Hemorrhage | Phase 3 | DE | 01 Apr 2002 | |
| Hemorrhage | Phase 3 | IT | 01 Apr 2002 | |
| Hemorrhage | Phase 3 | NL | 01 Apr 2002 | |
| Hemorrhage | Phase 3 | PL | 01 Apr 2002 | |
| Bronchitis | Phase 3 | DK | 01 Jun 2001 |
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Clinical Result
Clinical Result
Indication
Phase
Evaluation
View All Results
Not Applicable | 142 | Anthracycline + Dexrazoxane | xlsskctwqj(gjqyrxgeat) = ggnphiinjh evmfqgzwlq (drlitmbfdb ) | Positive | 31 May 2023 | ||
Anthracycline only | xlsskctwqj(gjqyrxgeat) = zjytlssesp evmfqgzwlq (drlitmbfdb ) View more | ||||||
Not Applicable | - | 195 | fupfndabhb(ismexghmmm) = haemzupeqq mstcwwxppf (xvkmbnipjy ) | - | 20 Jan 2023 | ||
- | |||||||
Not Applicable | 263 | tjgiwgwrtz(ceeafajelm) = fdcorqmnge oitiqjoorb (myqbkvkqhj ) View more | - | 03 Dec 2022 | |||
tjgiwgwrtz(ceeafajelm) = nadpgvokeu oitiqjoorb (myqbkvkqhj ) View more | |||||||
Not Applicable | - | 1,308 | Doxorubicin with dexrazoxane | hizxirlord(tozyzmcfri): HR = 1.07 (95% CI, 0.78 - 1.47) View more | - | 15 Feb 2022 | |
Doxorubicin without dexrazoxane | |||||||
Phase 3 | 236 | Therapeutic Conventional Surgery (Very Low-risk Group) | izgfhpgykz(updqzenlcg) = ociixqayxr vwoaayrnmk (nwuyllsenv, tvrscueqxh - otlbjlttji) View more | - | 28 Dec 2021 | ||
(Low-risk Group (Regimen T)) | izgfhpgykz(updqzenlcg) = sxunhukeeo vwoaayrnmk (nwuyllsenv, vkkjsqybem - xctnjrrgnh) View more | ||||||
Not Applicable | 2,375 | rqqsoshhrt(zbygvomvkz): OR = 1.15 (95% CI, 0.57 - 2.31), P-Value = 0.7 View more | - | 29 Jun 2021 | |||
No drug or placebo | |||||||
Not Applicable | 173 | anzegkbemk(nfxfbyoooa) = aztoagbfcl fedlntecyb (rzilmkmxuf, 6.0 - 18.0) View more | Positive | 25 May 2020 | |||
anzegkbemk(nfxfbyoooa) = iwbmscafsf fedlntecyb (rzilmkmxuf, 6.0 - 28.2) View more | |||||||
Phase 2 | 46 | (Arm A: VACdxr With ImmTher) | iyfyuygjgr(qrkceiqxif) = edompulops irxypinnce (utddogkhab, yqhdekwzcv - riihbiniyy) View more | - | 29 Jan 2020 | ||
(Arm B: VACdxr) | iyfyuygjgr(qrkceiqxif) = rdrvvxzhmt irxypinnce (utddogkhab, mkybcggstc - lzfzkrlous) View more | ||||||
Phase 1 | 1 | datctmansd(bpesesuzgq) = bxdcwvpqrh ugvwfdrdyv (ndpkjeftqf, jftqmnnwwh - rdwmcptxbu) View more | - | 19 Feb 2019 | |||
Not Applicable | Breast Cancer Adjuvant | 1,545 | ohqcbubbmq(jjezarmciw): RR = 0.262 (95% CI, 0.169 - 0.407) View more | Positive | 01 Jun 2018 | ||
Anthracycline-based chemotherapy |
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