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Chemical Structure| 908-54-3 Chemical Structure| 908-54-3

Structure of Diminazene aceturate
CAS No.: 908-54-3

Chemical Structure| 908-54-3

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Diminazene Aceturate is a di-amidine used as an effective trypanocidal agent.

Synonyms: Diminazene diaceturate; Diminazene (aceturate)

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Product Details of Diminazene aceturate

CAS No. :908-54-3
Formula : C22H29N9O6
M.W : 515.52
SMILES Code : N=C(N)C1=CC=C(/N=N/NC2=CC=C(C=C2)C(N)=N)C=C1.O=C(O)CNC(C)=O.O=C(O)CNC(C)=O
Synonyms :
Diminazene diaceturate; Diminazene (aceturate)
MDL No. :MFCD00058386
InChI Key :OKQSSSVVBOUMNZ-UHFFFAOYSA-N
Pubchem ID :5284544

Safety of Diminazene aceturate

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Trypanosoma equiperdum 5 μM 60 minutes Promotes linearization of mitochondrial minicircle DNA, forming DNA-protein complexes PMC53387
NRCMs 100 nM 48 hours To evaluate the protective effect of DIZE on PM2.5-induced cardiomyocyte apoptosis. Results showed that DIZE pretreatment upregulated ACE2 expression and suppressed Bax/Bcl-2 and cleaved caspase3/total caspase3 ratios, alleviating PM2.5-induced cardiomyocyte apoptosis. PMC9089227
Human CD34+ cells 100 nM 10 hours To evaluate the effect of DIZE on the migratory capacity of CD34+ cells from PH patients, results showed significant improvement in migration PMC3733435
Recombinant human ACE2 100 μM To evaluate the effect of DIZE on ACE2 enzymatic activity, results showed a twofold increase in ACE2 activity PMC3733435
Primary cultured human retinal pigment epithelia (hRPE) 10 μg/mL 6 hours DIZE significantly increased the expression of ACE2 and inhibited the expression of IL-6, IL-8, and MCP-1 at both mRNA and protein levels in LPS-stimulated RPE cell lines. PMC4748536
ARPE-19 cells 10 μg/mL 6 hours DIZE significantly increased the expression of ACE2 and inhibited the expression of IL-6, IL-8, and MCP-1 at both mRNA and protein levels in LPS-stimulated RPE cell lines. PMC4748536

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice PM2.5-induced cardiac dysfunction model Intraperitoneal injection 15 mg/kg/day Once daily for 30 days To evaluate the therapeutic effect of DIZE on PM2.5-induced cardiac dysfunction. Results showed that DIZE treatment significantly reversed PM2.5-induced reduction in ejection fraction and fractional shortening, reduced cardiomyocyte apoptosis, upregulated cardiac ACE2 expression, and decreased Bax/Bcl-2 and cleaved caspase3/total caspase3 ratios. PMC9089227
Mice Tg2576 mouse model Intraperitoneal injection 15 mg/kg/day Daily for 30 days or 10 weeks DIZE, by enhancing ACE2 activity, reduced hippocampal Aβ pathology and restored cognitive function. In symptomatic aged Tg2576 mice, DIZE restored cognitive function; in pre-symptomatic young mice, DIZE prevented the onset of cognitive impairment. PMC7035243
C57BL/6 mice Repeated LPS-induced neuroinflammation model Intraperitoneal injection 15 mg/kg Daily administration for 2 weeks To evaluate the neuroprotective effects of DIZE via activation of ACE2/Ang(1–7)/MasR axis in neuroinflammation. Results demonstrated that DIZE treatment significantly attenuated LPS-induced overactivation of ACE/AngII/AT1 axis, restored the balance of ACE2/Ang(1–7)/MasR axis, and suppressed microglial proinflammatory polarization through FOXO1-autophagy pathway. PMC8520723
Rats Myocardial infarction model Subcutaneous injection 15 mg/kg/day Once daily, continued throughout the study period DIZE treatment attenuated the MI-induced decrease in cardiac function, improved hemodynamic function, reduced ventricular hypertrophy, and restored the normal balance of the cardiac renin-angiotensin system. PMC3881360
Ldlr−/− mice AngII-induced abdominal aortic aneurysms Intramuscular injection 30 mg/kg/day Daily for 28 days DIZE significantly decreased aortic lumen diameters and aortic external diameters of AngII-infused mice resulting in a marked reduction in AAA incidence (from 73 to 29%). None of these effects of DIZE were observed in the Ace2?/y mice. PMC4250973
Sprague Dawley rats Endothelin-1-induced ischemic stroke model Intraperitoneal injection 0.75, 2.5, 7.5, 15 mg/kg Administered at 4h, 1d, and 2d post-stroke To evaluate the neuroprotective effects of Diminazene aceturate post-stroke. Results showed that 7.5 mg/kg dose significantly reduced infarct volume and improved neurological function. PMC4465873

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01477749 Cancer of Prostate ... More >> Cancer of the Prostate Neoplasms, Prostate Neoplasms, Prostatic Prostate Cancer Prostate Neoplasms Prostatic Cancer Less << Phase 2 Completed - Austria ... More >> Ludwig Boltzmann-Institute for Applied Cancer Research Wien, Austria, A-1100 France Department of Cancer Medicine and Genitourinary Oncology Group Institut Gustave Roussy (IGR) Département de médicine Vaillant, Villejuif Cedex, France, 94805 Netherlands Radboud University Nijmegen; UMC St Radboud Hospital; Faculteit der Medische Wetenschappen, Urologie Nijmegen, Gelderland, Netherlands, 6525 GA United Kingdom Barts Cancer Institute - a Cancer Research UK Centre of Excellence, Queen Mary University of London London, United Kingdom, EC1M 6BQ Less <<
NCT02983344 Femoral Fracture Not Applicable Completed - Malaysia ... More >> Kuala Lumpur General Hospital Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50586 Less <<
NCT01250509 Obesity Phase 2 Completed - United States, California ... More >> UCSF Osher Center for Integrative Medicine San Francisco, California, United States, 94115 Less <<
NCT01477749 - Completed - -
NCT02373137 Keratoplasty ... More >>Grafting, Corneal Transplantation, Corneal Transplantation, Cornea Keratoplasty, Lamellar Less << Phase 4 Active, not recruiting December 2019 United States, California ... More >> Byers Eye Institute, Stanford University Palo Alto, California, United States, 94303 F. I. Proctor Foundation, University of California, San Francisco San Francisco, California, United States, 94143 United States, Oregon Casey Eye Institute, Oregon Health & Science University Portland, Oregon, United States, 97239 Less <<
NCT02235051 Cancer Survivor ... More >> Estrogen Receptor-positive Breast Cancer Stage IA Breast Cancer Stage IB Breast Cancer Stage IIA Breast Cancer Stage IIB Breast Cancer Stage IIIA Breast Cancer Postmenopausal Less << Not Applicable Active, not recruiting September 2019 United States, California ... More >> City of Hope Medical Center Duarte, California, United States, 91010 Less <<
NCT01250509 - Completed - -
NCT01674439 Craniofacial Microsomia Phase 2 Completed - Brazil ... More >> Division of Plastic and Reconstructive Surgery Sao Paulo, SP, Brazil, 01246000 Less <<
NCT01218750 Diffuse Diabetic Macular Edema Not Applicable Unknown December 2011 Poland ... More >> Military Institute of Medicine Recruiting Warsaw, Szaserów 44, Poland, 04-141 Contact: Kowal Ewelina    (+48) 22 665 707 584    ekowal@wim.mil.pl    Principal Investigator: Robaszkiewicz Jacek, dr med.          Sub-Investigator: Chmielewska I. Katarzyna, lek. med. Less <<
NCT02073266 Macular Holes ... More >> Visual Acuity Gain Cataract Complications Less << Not Applicable Completed - Canada, Quebec ... More >> Centre universitaire d'ophtalmologie, Hôpital du Saint-Sacrement, CHU de Québec Québec, Quebec, Canada, G1S 4L8 Less <<
NCT01228188 Macular Holes Not Applicable Unknown August 2013 Poland ... More >> Military Institute of Medcine Recruiting Warsaw, ul. Szaserów 128, Poland, 04-141 Contact: Połeć Dorota, mgr    + 48 22 681 67 35    dpolec@wim.mil.pl    Principal Investigator: Robaszkiewicz Jacek, dr med.          Sub-Investigator: Chmielewska I. Katarzyna, lek. med.          Sub-Investigator: Karpińska Urszula, lek. med. Less <<
NCT00302328 Idiopathic Macular Hole Not Applicable Completed - Denmark ... More >> Department of Ophthalmology, Glostrup Hospital Copenhagen, Denmark, DK-2600 Less <<
NCT02126280 - Completed - Russian Federation ... More >> Institute for Atherosclerosis Research Moscow, Russian Federation, 121609 Less <<
NCT01485575 - Recruiting June 2020 Austria ... More >> General Hospital Linz Recruiting Linz, Austria, 4010 Contact: Rupert W Strauss, MD    +43 732 7806 - 73425    rupert.strauss@akh.linz.at    Switzerland St. Gallen Hospital Recruiting St. Gallen, SG, Switzerland, 9007 Contact: Christophe Valmaggia, MD    +41 71 494 11 11    Christophe.Valmaggia@kssg.ch    Kantonsspital Winterthur, Eye Clinic Recruiting Winterthur, Switzerland, 8401 Contact: Paul B Henrich, MD    +41 52 266 28 95    bernhard.henrich@ksw.ch Less <<
NCT01385878 Cataract Not Applicable Unknown December 2011 India ... More >> Iladevi Cataract & IOL Research Centre Recruiting Ahmedabad, Gujarat, India, 380009 Contact: Abhay r Vasavada, MS,FRCS       icirc@abhayvasavada.com    Principal Investigator: Abhay R Vasavada, MS, FRCS Less <<
NCT02466256 Cataract Not Applicable Completed - -
NCT03755752 Cataract Diabetic Not Applicable Completed - Egypt ... More >> Faculty of Medicine Assiut, Egypt, 71515 Less <<
NCT01621789 Cataract Phase 3 Completed - Brazil ... More >> Dept. of Ophthalmology - UNIFESP/Hospital São Paulo São Paulo, SP, Brazil, 04023-062 Less <<
NCT00302328 - Completed - -
NCT00757380 Idiopathic Epiretinal Membrane... More >>s Less << Not Applicable Completed - Austria ... More >> The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery Vienna, Austria, 1030 Less <<
NCT00419185 Idiopathic Macular Hole Not Applicable Completed - Germany ... More >> Eye Clinic, University Schleswig-Holstein, Campus Lübeck Lübeck, Schleswig-Holstein, Germany, 23538 Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.94mL

0.39mL

0.19mL

9.70mL

1.94mL

0.97mL

19.40mL

3.88mL

1.94mL

References

[1]de Koning HP, Anderson LF, et al. The trypanocide diminazene aceturate is accumulated predominantly through the TbAT1 purine transporter: additional insights on diamidine resistance in african trypanosomes. Antimicrob Agents Chemother. 2004 May;48(5):1515-9.

[2]Tuntasuvan D, Jarabrum W, et al. Chemotherapy of surra in horses and mules with diminazene aceturate. Vet Parasitol. 2003 Jan 2;110(3-4):227-33.

[3]Kuriakose S, Muleme HM, Onyilagha C, Singh R, Jia P, Uzonna JE. Diminazene aceturate (Berenil) modulates the host cellular and inflammatory responses to Trypanosoma congolense infection. PLoS One. 2012;7(11):e48696

[4]Castardeli C, Sartório CL, Pimentel EB, Forechi L, Mill JG. The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular diastolic dysfunction following myocardial infarction in rats. Biomed Pharmacother. 2018 Nov;107:212-218

[5]Duan R, Xue X, Zhang QQ, Wang SY, Gong PY, E Y, Jiang T, Zhang YD. ACE2 activator diminazene aceturate ameliorates Alzheimer's disease-like neuropathology and rescues cognitive impairment in SAMP8 mice. Aging (Albany NY). 2020 Jul 23;12(14):14819-14829

[6]de Brito MG, Mengarda AC, Oliveira GL, Cirino ME, Silva TC, de Oliveira RN, Allegretti SM, de Moraes J. Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection. Antimicrob Agents Chemother. 2020 Oct 20;64(11):e01372-20

[7]Souza-Silva TG, Vilas-Boas DF, Gonçalves-Santos E, Mazzeti AL, Caldas IS, Gonçalves RV, Diniz LF, Novaes RD. Impact of diminazene aceturate on renin-angiotensin system, infectious myocarditis and skeletal myositis in mice: An in vitro and in vivo study. Life Sci. 2020 Sep 15;257:118067

 

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