Diminazene 

Diminazene is an antiparasitic agent widely used to treat parasitic diseases caused by hemoparasites (such as trypanosomes and babesia). Diminazene acts as an ACE2 activator and exerts cardiovascular protective effects by activating the ACE2/Ang-(1-7)/Mas receptor axis. By regulating gut microbiota-tryptophan metabolism, Diminazene inhibits the activation of core inflammatory signaling pathways including MAPK, STAT and NF-κB, increases central 5-HT levels, and suppresses splenic TNF-α production, thereby alleviating systemic inflammation^{[1][2][3][4][5][6]}.

Diminazene downregulates lipopolysaccharide-induced proinflammatory cytokine production in macrophages by inhibiting the phosphorylation of MAPK/ERK and STAT proteins^[1].
Diminazene activates the ACE2/Ang (1-7)/Mas axis, thereby stimulating vascular repair-related functions in CD34⁺ cells^[1].
Diminazene (100 μM; 5 min) reduces non-induced arrhythmic contractions in isolated ventricular cardiomyocytes from C57bl6/J mice, while increasing the maximal contraction and relaxation rates, but exerts no effect on fractional shortening or systolic/diastolic duration parameters^[2].
Diminazene (100 μM; 5 min) shortens the action potential duration of all repolarization phases in isolated ventricular myocytes from C57bl6/J mice, induces resting membrane hyperpolarization, and inhibits the halothane+isoproterenol-induced prolongation of action potential, but exerts no effect on the action potential amplitude or the halothane-induced reduction in the maximum upstroke velocity of action potential^[2].
Diminazene inhibits the phosphorylation of MAPKs (ERK, p38, JNK), STAT1, STAT3 and NF-κB p65, while upregulating the expression of SOCS1 and SOCS3, and downregulating the production of proinflammatory cytokines in primary bone marrow-derived macrophages and dendritic cells without altering the expression of TLRs^[4].
Diminazene specifically binds to adenine-thymidine-rich sites in kinetoplast DNA of trypanosomes, induces irreversible akinetoplastic damage, disrupts chromatin structure during the G₂ phase of the cell cycle, and inhibits DNA replication by interfering with the binding of DNA topoisomerase and DNA conformation^[4].
Diminazene (3.12-200 μM; 24-120 h) potently kills immature cercariae of *Schistosoma mansoni* in a time- and concentration-dependent manner, with an EC₅₀ of 6.4 μM after 120 h of incubation^[6].
Diminazene (3.12-200 μM; 24-120 h) kills paired adult Schistosoma mansoni in a time- and concentration-dependent manner, with an EC₅₀ of 24.2 μM at 120 h^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Diminazene (5-15 mg/kg; i.v., p.o., s.c., single administration or long-term administration) exerts beneficial effects including reducing blood pressure, improving vascular endothelial and diastolic functions, protecting the heart and kidneys, regulating immunity, and inhibiting excessive inflammatory responses in various animal models of diseases^[1].
Diminazene (5 mg/kg; i.v.; single administration) reduces halothane-epinephrine induced arrhythmic events in rats by approximately 68%, and its effect is independent of Mas receptor activation and nitric oxide release^[2].
Diminazene (15 mg/kg; s.c.; single administration) non-significantly reduces the 48-hour mortality rate to 38.5% in a rat model of septic cardiomyopathy, improves cardiac function, decreases the levels of inflammatory and myocardial injury biomarkers, restores the balance of the myocardial renin-angiotensin system, and alleviates myocardial structural damage^[3].
Diminazene modulates host immune responses, reduces the production of proinflammatory cytokines, controls parasitemia, enhances the production of parasite-specific antibodies, and induces protective immunity against homologous Trypanosoma congolense challenge in infected mice^[4].
Pretreatment with Diminazene inhibits LPS (HY-D1056)-induced production of proinflammatory cytokines by suppressing the phosphorylation of MAPK and STAT and upregulating SOCS proteins, thereby ameliorating acute inflammation and mortality in LPS-challenged mice^[4].
Chronic administration of Diminazene prevents and blocks experimental pulmonary hypertension, and upregulates the expression of ACE II mRNA in rats treated with Bleomycin (HY-108345) and Monocrotaline (HY-N0750)^[4].
Diminazene (2 mg/kg; i.p.; single administration) reduces the production of TNF in serum and spleen by restoring intestinal ACE2 function, elevating central 5-HT levels, and activating the efferent sympathetic branch of the inflammatory reflex, thereby alleviating systemic inflammatory responses in male C57BL/6 mice with endotoxemia^[5].
Diminazene (10-400 mg/kg; i.p., p.o.; single administration) reduces worm burden, egg production, hepatosplenomegaly severity and liver injury markers in mice with chronic S. mansoni infection in a dose- and route-dependent manner, with an ED₅₀ of 44.6 mg/kg for intraperitoneal injection and 226.8 mg/kg for oral administration^[6].
Diminazene (100-400 mg/kg; i.p., p.o.; single administration) causes a significant moderate reduction in worm burden in mice with early-stage Schistosoma mansoni infection, while reducing egg production, but fails to alleviate hepatosplenomegaly in this model^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

281.32

C₁₄H₁₅N₇

536-71-0

N=C(C1=CC=C(C=C1)/N=N/NC2=CC=C(C(N)=N)C=C2)N

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Qaradakhi T, et al. The potential actions of angiotensin-converting enzyme II (ACE2) activator diminazene aceturate (DIZE) in various diseases. Clin Exp Pharmacol Physiol. 2020;47(5):751-758.

  [2]. Joviano-Santos JV, et al. Diminazene aceturate (DIZE) has cellular and in vivo antiarrhythmic effects. Clin Exp Pharmacol Physiol. 2020;47(2):213-219.

  [3]. Lu Z, et al. Diminazene aceturate mitigates cardiomyopathy by interfering with renin-angiotensin system in a septic rat model. BMC Pharmacol Toxicol. 2022;23(1):44. Published 2022 Jul 4.

  [4]. Kuriakose S, et al. Diminazene aceturate (Berenil), a new use for an old compound?. Int Immunopharmacol. 2014;21(2):342-345.  [Content Brief]

  [5]. Passaglia P, et al. Diminazene aceturate attenuates systemic inflammation via microbiota gut-5-HT brain-spleen sympathetic axis in male mice. Brain Behav Immun. 2024;119:105-119.

  [6]. de Brito MG, et al. Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection. Antimicrob Agents Chemother. 2020;64(11):e01372-20. Published 2020 Oct 20.