Last update 30 Jun 2024
Dexrazoxane Hydrochloride
Last update 30 Jun 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), |
RegulationAccelerated Approval (US), Orphan Drug (US), Orphan Drug (AU) |
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Structure
Molecular FormulaC11H17ClN4O4 |
InChIKeyBIFMNMPSIYHKDN-FJXQXJEOSA-N |
CAS Registry149003-01-0 |
Related
51
Clinical Trials associated with Dexrazoxane HydrochlorideANTICIPATE: 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
A Phase I Study of Venetoclax in Combination With Cytotoxic Chemotherapy, Including Calaspargase Pegol, for Children, Adolescents and Young Adults With High-Risk Hematologic Malignancies
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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822
Literatures (Medical) associated with Dexrazoxane Hydrochloride01 Apr 2024Redox biology
Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy
Article
Author: Guo, Yishan ; Wang, Li ; Xiang, Ying ; Yang, Jinru ; Sun, Guogen ; Jin, Min ; Zhang, Tao ; Han, Bing ; Li, Jiao ; Huang, Chuying ; Wu, Bo ; Li, Tuo ; Zhou, Yong ; Wei, Yumiao ; Mao, Yong ; Hu, Jiaxing ; Qiu, Jiao ; Tan, Yong ; Li, Shuijie ; Wang, Yongsheng ; Wang, Yuqi ; Lei, Lingshan ; Huang, Rui ; Song, Xiusheng
Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin.
09 Jan 2024Advances in pharmacological and pharmaceutical sciences
Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable
Article
Author: Ahmed, Mustapha A ; Zoiku, Felix K ; Adokoh, Christian K ; Armah, Francis A ; Ghartey-Kwansah, George ; Fynn, Patrick M ; Ameyaw, Elvis O ; Asiamah, Isaac ; Ofori-Attah, Ebenezer
Background. The emergence of drug-resistant parasites impedes disease management and eradication efforts. Hence, a reinvigorated attempt to search for potent lead compounds in the mangroves is imperative. Aim. This study evaluates in vitro antiplasmodial activity, antioxidant properties, and cytotoxicity of A. africana leaf alkaloidal extracts. Methods. The A. africana leaves were macerated with 70% ethanol to obtain a total crude extract. Dichloromethane and chloroform-isopropanol (3 : 1, v/v) were used to extract the crude alkaloids and quaternary alkaloids from the total crude. The antiplasmodial activities of the alkaloidal extracts were performed against 3D7 P. falciparum chloroquine-sensitive clone via the SYBR Green I fluorescence assay with artesunate serving as the reference drug. The alkaloidal extracts were further evaluated for antioxidant properties via the total antioxidant capacity (TAC), the total glutathione concentration (GSH), the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and the ferric-reducing antioxidant power (FRAP) methods. The cytotoxic activity of the alkaloidal extracts was tested on erythrocytes using a 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide-MTT assay with little modification. The phytocompounds in the alkaloidal extracts were identified via gas chromatography-mass spectrometry (GC-MS) techniques. Results. The total crude extract showed good antiplasmodial activity (IC50 = 11.890 µg/mL). The crude and quaternary alkaloidal extracts demonstrated promising antiplasmodial effects with IC50 values of 6.217 and 6.285 µg/mL, respectively. The total crude and alkaloidal extracts showed good antioxidant properties with negligible cytotoxicity on erythrocytes with good selectivity indices. The GC-MS spectral analysis of crude alkaloidal extracts gave indole and isoquinoline alkaloids and several other compounds. Dexrazoxane was found to be the main compound predicted, with an 86% peak area in the quaternary alkaloidal extract. Conclusion. The crude and quaternary alkaloidal extracts exhibited antiplasmodial activities and ability to inhibit oxidative stress with negligible toxicity on erythrocytes. This may be good characteristics to avoid oxidative stress related to Plasmodium infection in the treatment of malaria.
01 Jan 2024British journal of pharmacology
Novel metallo‐β‐lactamases inhibitors restore the susceptibility of carbapenems to New Delhi metallo‐lactamase‐1 (NDM‐1)‐harbouring bacteria
Article
Author: Gao, Yawen ; Yang, Mengge ; Wang, Jianfeng ; Ding, Rui ; Qiu, Jiazhang ; Niu, Xiaodi ; Liu, Hongtao ; Guo, Yan ; Feng, Haihua ; Deng, Xuming
Abstract:
Background and purpose:
The production of metallo‐β‐lactamases is a major mechanisms adopted by bacterial pathogens to resist carbapenems. Repurposing approved drugs to restore the efficacy of carbapenems represents an efficient and cost‐effective approach to fight infections caused by carbapenem resistant pathogens.
Experimental approach:
The nitrocefin hydrolysis assay was employed to screen potential New Delhi metallo‐lactamase‐1 (NDM‐1) inhibitors from a commercially available U.S. Food and Drug Administration (FDA) approved drug library. The mechanism of inhibition was clarified by metal restoration, inductively coupled plasma mass spectrometry (ICP‐MS) and molecular dynamics simulation. The in vitro synergistic antibacterial effect of the identified inhibitors with meropenem was determined by the checkerboard minimum inhibitory concentration (MIC) assay, time‐dependent killing assay and combined disc test. Three mouse infection models were used to further evaluate the in vivo therapeutic efficacy of combined therapy.
Key results:
Twelve FDA‐approved compounds were initially screened to inhibit the ability of NDM‐1 to hydrolyse nitrocefin. Among these compounds, dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid were demonstrated to inhibit all tested metallo‐β‐lactamases and showed an in vitro synergistic bactericidal effect with meropenem against metallo‐β‐lactamases‐producing bacteria. Dexrazoxane, embelin and candesartan cilexetil are metal ion chelating agents, while the inhibition of NDM‐1 by nordihydroguaiaretic acid involves its direct binding to the active region of NDM‐1. Furthermore, these four drugs dramatically rescued the treatment efficacy of meropenem in three infection models.
Conclusions and implications:
Our observations indicated that dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid are promising carbapenem adjuvants against metallo‐β‐lactamases‐positive carbapenem resistant bacterial pathogens.
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 | ycqmzrjheq(gxmvkrqsfm) = wpohbpejba esntedczce (wcpwrzfzla ) | Positive | 31 May 2023 | ||
Anthracycline only | ycqmzrjheq(gxmvkrqsfm) = nfesqvwxub esntedczce (wcpwrzfzla ) View more | ||||||
Not Applicable | - | 195 | imabfzlroy(tlyxgotwtb) = xyxgwmabdo skypnuwqhn (fdmxgzuroa ) | - | 20 Jan 2023 | ||
- | |||||||
Not Applicable | 263 | oiutazjasv(jzzeyjiwgc) = otkfybwpae llbcpwywwe (rbrcagaevg ) View more | - | 03 Dec 2022 | |||
oiutazjasv(jzzeyjiwgc) = lhkmrpyzot llbcpwywwe (rbrcagaevg ) View more | |||||||
Not Applicable | - | 1,308 | Doxorubicin with dexrazoxane | nkstspdciq(dogirhtmzq): 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) | ooxokprsxq(rtqlwecdly) = fyxdnsixoj oxbbtmacvf (wpouyqjecr, rxnvwzvtur - mbjicemsiq) View more | - | 28 Dec 2021 | ||
(Low-risk Group (Regimen T)) | ooxokprsxq(rtqlwecdly) = sazkshqrua oxbbtmacvf (wpouyqjecr, fvvlnefuak - eyyyzujvlo) View more | ||||||
Not Applicable | 2,375 | gvyuiycwvy(hygyytamsw): 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 | jcknhfkiyc(zatmeauunx) = kmllxyjjsb kznsxknsfa (hlhvegsktb, 6.0 - 18.0) View more | Positive | 25 May 2020 | |||
jcknhfkiyc(zatmeauunx) = fsflaphsoq kznsxknsfa (hlhvegsktb, 6.0 - 28.2) View more | |||||||
Phase 2 | 46 | (Arm A: VACdxr With ImmTher) | neiimeafzp(tlaaoranty) = vnmpdtlaue gdyrycgihd (wsijyhbytw, zzgxdgzhhi - qxgnrbfclg) View more | - | 29 Jan 2020 | ||
(Arm B: VACdxr) | neiimeafzp(tlaaoranty) = xgndwsetwn gdyrycgihd (wsijyhbytw, tbrkkjkbja - vtwwluumdx) View more | ||||||
Phase 1 | 1 | zelfhsrrhk(kyxqwfqlos) = gayqaqoqkv nrdhwybxfi (xzfvnxmovb, ubinorcslv - dsmbijktzt) View more | - | 19 Feb 2019 | |||
Not Applicable | Breast Cancer Adjuvant | 1,545 | zahoqlgjvw(owycbuamll): RR = 0.262 (95% CI, 0.169 - 0.407) View more | Positive | 01 Jun 2018 | ||
Anthracycline-based chemotherapy |
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