Mdivi-1, derivative of quinazolinone, is a selective inhibitor of mitochondrial division by targeting Dnm1 (dynamin-1) and DRP (dynamin-related protein).
In mammalian cells (COS cell), mdivi-1 inhibits mitochondrial division with IC50 of 50 μM by specially inhibiting DRP1 activity, and in Hela cell, mdivi-1 impedes apoptosis early in the intrinsic pathway by attenuating Bak/Bax dependent MOMP (mitochondrial outer membrane permeabilization)[3].
It has been shown to reduce seizure activity and increase survival of KA-reduced mice intravenously injected of 20 mg/kg mdivi-1 by protecting mitochondrial morphology and attenuating cell death in the hippocampus[4]. In the study of ischemia reperfusion injury, mdivi-1 can protect against ischemia reperfusion injury of spinal cord neurons and mitochondrial dysfunction in vivo through activating BK channels dependently in SD rat which were treated with intravenous bolus of 1 mg/kg[5]. The function of mdivi-1 is also reflected in the protection of ischemic retina. Research has shown that mdivi-1 can reverse cell apoptosis caused by transient retinal ischemia and significantly increase the number and survival of retinal ganglia cells by approximately 54% in 3-month-old C57BL/6 mice (intraperitoneal injection, 50 mg/kg). In addition, mdivi-1 treatment did not affect the increase of Drp1 protein expression, but obviously down-regulate the expression of GFAP[6].
Multiple roles of mdivi-1, such as reduces animal blood pressure, alleviate traumatic brain injury induced brain damage[7], and protect against doxorubicin-induced cardiotoxicity, have confirmed by relevant experiments[8]. In general, mdivi-1 provides a new treatment for stroke, myocardial infarction and neurodegenerative diseases.
Mdivi-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293 cells
50 µM
overnight
Mdivi-1 was used to inhibit DRP1 and study the effect of GJA1-20k on mitochondrial fission. The results showed that GJA1-20k could induce mitochondrial fission through actin polymerization independently of DRP1.
Elife. 2021 Oct 5;10:e69207.
H460 and H1299 cells
15 μM
96 h
To inhibit mitophagy and evaluate its effect on cell viability after shUSP35 infection
Clin Transl Med. 2021 Apr;11(4):e390.
A172 glioma cells
1, 5, and 10 μM
2 h
To assess changes in mitochondrial length and pregnenolone (P5) concentration. Results showed that MDIVI-1 dose-dependently increased mitochondrial length and P5 concentration.
Cells. 2020 Oct 19;9(10):2323.
A172 glioma cells
5 μM
24 h
To evaluate the rhythmic changes in P5 and TSPO protein levels after chronic MDIVI-1 treatment. Results showed that MDIVI-1 treatment abolished the rhythmic variations of P5 and TSPO.
Cells. 2020 Oct 19;9(10):2323.
NIH3T3 cells
10 μM
Mdivi-1 significantly reduced caffeine-induced autophagosome formation, indicating that Mdivi-1 inhibits autophagy by preventing mitochondrial fission.
Theranostics. 2018 Nov 10;8(20):5713-5730.
NIH3T3 cells
10 µM
Mdivi-1, a mitophagy inhibitor that prevents mitochondria fission, dramatically reduced the caffeine-induced autophagosome formation
Theranostics. 2018 Nov 10;8(20):5713-5730.
primary cortical neurons
50 μM
1 h
Mdivi-1 significantly inhibited basal and maximal respiration, indicating its inhibitory effect on mitochondrial Complex I-dependent respiration.
Dev Cell. 2017 Mar 27;40(6):583-594.e6.
COS-7 cells
50 μM
1 h
Mdivi-1 significantly inhibited basal and maximal respiration, indicating its inhibitory effect on mitochondrial Complex I-dependent respiration.
Dev Cell. 2017 Mar 27;40(6):583-594.e6.
Drp1 KO MEFs
50 μM
16 min
Mdivi-1 inhibited maximal respiration, indicating its inhibitory effect on mitochondrial Complex I-dependent respiration, independent of Drp1.
Dev Cell. 2017 Mar 27;40(6):583-594.e6.
vascular endothelial cells (ECs)
5 μM
Mdivi-1 reduced Aβ-induced apoptosis of ECs by inhibiting mitochondrial fission, indicating that Aβ-induced mitochondrial fission is essential for ECs apoptosis.
Aging Cell. 2025 Feb;24(2):e14374.
Mdivi-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
UV-induced skin damage model
Intraperitoneal injection
1.5 mg/kg
Once daily for 6 weeks
Mdivi-1 blocked the protective effect of caffeine on UV-induced skin damage, indicating that Mdivi-1 attenuates the protective effect of caffeine by inhibiting mitophagy.
Theranostics. 2018 Nov 10;8(20):5713-5730.
Mice
UV irradiation-induced skin damage model
Intraperitoneal injection
1.5 mg/kg
Once daily for 6 weeks
Inhibited UV-induced skin damage
Theranostics. 2018 Nov 10;8(20):5713-5730.
Mice
APP/PS1 mice
Not specified
50 mg/kg
Twice a week for 4 weeks
Mdivi-1 effectively attenuated bone blood vessels injury and bone formation in APP/PS1 mice, indicating that Aβ-induced mitochondrial fission plays a critical role in bone blood vessels injury.
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