A4472-10mg | Mdivi 1 [338967-87-6] Clinisciences

Mdivi-1 is a selective cell-permeable inhibitor of mitochondrial division DRP1 (dynamin-related GTPase) and mitochondrial division Dynamin I (Dnm1). DRP1, a member of the dynamin family of large GTPases, mediates mitochondrial fission.

In vitro: The most efficacious inhibitor, mdivi-1 attenuates mitochondrial division in yeast and mammalian cells by selectively inhibiting the mitochondrial Drp1-mediated division dynamin. Mdivi-1 potently blocks Bid-activated Bax/Bak-dependent cytochrome c release from mitochondria [1].

In vivo: Mdivi-1 treatment blocked apoptotic cell death in ischemic retina, and significantly increased RGC survival at 2 weeks after ischemia. Moreover, Mdivi-1 treatment did not change this increase of Drp1 protein expression but significantly decreased GFAP protein expression [2].

Clinical trial: Currently no clinical data are available.

References:
[1] Cassidy-Stone A, Chipuk JE, Ingerman E, Song C, Yoo C, Kuwana T, Kurth MJ, Shaw JT, Hinshaw JE, Green DR, Nunnari J. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008;14(2):193-204.
[2] Park SW, Kim KY, Lindsey JD, Dai Y, Heo H, Nguyen DH, Ellisman MH, Weinreb RN, Ju WK. A selective inhibitor of drp1, mdivi-1, increases retinal ganglion cell survival in acute ischemic mouse retina. Invest Ophthalmol Vis Sci. 2011;52(5):2837-43.

1. Mohamed Hessien, et al. "Inhibition of Drp1 orchestrates the responsiveness of breast cancer cells to paclitaxel but insignificantly relieves paclitaxel-related ovarian damage in mice." Sci Rep. 2023 Dec 20;13(1):22782. PMID: 38129495

2. Weiwei Qin, Xiyang Tong, et al. "Preservation of mitochondrial homeostasis is responsible for the ameliorative effects of Suhuang antitussive capsule on non-resolving inflammation via inhibition of NF-κB signaling and NLRP3 inflammasome activation." J Ethnopharmacol. 2021 May 10;271:113827. PMID: 33460751

3. Raja Gopal Reddy Mooli, Dhanunjay Mukhi, et al. "An indispensable role for dynamin-related protein 1 in beige and brown adipogenesis." J Cell Sci. 2020 Sep 15;133(18):jcs247593. PMID: 32843579

4. Qin W, Wu X, et al. "Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma." Biomed Pharmacother. 2019 Jul 14;118:109188. PMID: 31315072

5. Chien L, Liang MZ, et al. "Mitochondrial therapy promotes regeneration of injured hippocampal neurons." Biochim Biophys Acta. 2018 Jun 15. pii: S0925-4439(18)30216-3. PMID: 29913215

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	353.22
Cas No.	338967-87-6
Formula	C₁₅H₁₀C_l2N₂O₂S
Solubility	insoluble in H2O; insoluble in EtOH; ≥17.65 mg/mL in DMSO
Chemical Name	3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanylidene-1H-quinazolin-4-one
SDF	Download SDF
Canonical SMILES	COC1=C(C=C(C(=C1)N2C(=O)C3=CC=CC=C3NC2=S)Cl)Cl
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Cell experiment [1]:
Cell lines	Yeast cells harboring the temperature-sensitive fzo1-1 allele
Preparation method	The solubility of this compound in DMSO is >17.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	50 μM
Applications	Mdivi-1 (50 μM) inhibited mitochondrial division in mammalian cells (COS cells) by attenuating Drp1 self-assembly. Mdivi-1 (50 μM) attenuated mammalian mitochondrial division and Drp1 self-assembly during apoptosis. Mdivi-1 significantly inhibited STS-induced annexin V staining of non-necrotic cells as assessed by FACS analysis, indicating that mdivi-1 inhibited apoptosis.
Animal experiment [2]:
Animal models	C57BL/6 mice
Dosage form	Intraperitoneal injection, 50 mg/kg, 60 minutes
Application	Mdivi-1 treatment significantly increased RGC survival by approximately 54% in the central, 58% in the middle, and 48% in the peripheral areas. Mdivi-1 treatment significantly decreased GFAP protein expression in ischemic retina at 12 hours. Mdivi-1 treatment did not change mean arterial blood pressure, body weight, animal appearance or behavior.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Cassidy-Stone A, Chipuk J E, Ingerman E, et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization[J]. Developmental cell, 2008, 14(2): 193-204. [2]. Park S W, Kim K Y, Lindsey J D, et al. A selective inhibitor of drp1, mdivi-1, increases retinal ganglion cell survival in acute ischemic mouse retina[J]. Investigative ophthalmology & visual science, 2011, 52(5): 2837-2843.

Description	Mdivi 1 is a selective cell-permeable inhibitor of mitochondrial division dynamin-related GTPase (DRP1) and mitochondrial division dynamin I (Dnm1).
Targets	DRP1	Dnm1
IC50		1 - 10 µM