Mdivi-1
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MedKoo CAT#: 522436

CAS#: 338967-87-6

Description: Mdivi-1 is a selective cell-permeable inhibitor of mitochondrial division dynamin-related GTPase (DRP1) and mitochondrial division dynamin I (Dnm1). Mdivi-1 inhibits apoptosis by inhibiting mitochondrial outer membrane permeabilization. Mdivi-1 is the first selective inhibitor of mitochondrial division dynamins. Mdivi-1 represents a class of therapeutics for stroke, myocardial infarction, and neurodegenerative diseases.


Chemical Structure

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Mdivi-1
CAS# 338967-87-6

Theoretical Analysis

MedKoo Cat#: 522436
Name: Mdivi-1
CAS#: 338967-87-6
Chemical Formula: C15H10Cl2N2O2S
Exact Mass: 351.98
Molecular Weight: 353.217
Elemental Analysis: C, 51.00; H, 2.85; Cl, 20.07; N, 7.93; O, 9.06; S, 9.08

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 200 Ready to ship
50mg USD 350 Ready to ship
100mg USD 600 Ready to ship
200mg USD 1050 Ready to ship
500mg USD 2150 Ready to ship
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Synonym: Mdivi-1; Mdivi 1; Mdivi1; Mitochondrial Division Inhibitor 1

IUPAC/Chemical Name: 3-(2,4-dichloro-5-methoxyphenyl)-2-mercaptoquinazolin-4(3H)-one

InChi Key: NZJKEVWTYMOYOR-UHFFFAOYSA-N

InChi Code: InChI=1S/C15H10Cl2N2O2S/c1-21-13-7-12(9(16)6-10(13)17)19-14(20)8-4-2-3-5-11(8)18-15(19)22/h2-7H,1H3,(H,18,22)

SMILES Code: O=C1N(C2=CC(OC)=C(Cl)C=C2Cl)C(S)=NC3=C1C=CC=C3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Mdivi-1 is a selective dynamin-related protein 1 (Drp1) inhibitor.
In vitro activity: Time-lapse fluorescence microscopy revealed that mdivi-1 blocked NMDA-induced mitochondrial fission but not that triggered by sustained AMPA receptor activation, showing that mdivi-1 inhibits excitotoxic mitochondrial fragmentation in a source specific manner. Similarly, mdivi-1 strongly reduced NMDA-triggered necrotic-like neuronal death and, to a lesser extent, AMPA-induced toxicity. Interestingly, neuroprotection provided by mdivi-1 against NMDA, but not AMPA, correlated with a reduction in cytosolic Ca2+ ([Ca2+]cyt) overload and calpain activation indicating additional cytoprotective mechanisms. Reference: Front Mol Neurosci. 2018 Jan 17;11:3. https://pubmed.ncbi.nlm.nih.gov/29386996/
In vivo activity: C57BL/6 mice received injections of mdivi-1 (50 mg/kg) or vehicle, and then transient retinal ischemia was induced by acute IOP elevation. Drp1 and GFAP protein expression was significantly increased in the early neurodegenerative events (within 12 hours) of ischemic mouse retina. Mdivi-1 treatment blocked apoptotic cell death in ischemic retina, and significantly increased RGC survival at 2 weeks after ischemia. Reference: Invest Ophthalmol Vis Sci. 2011 Apr 27;52(5):2837-43. https://pubmed.ncbi.nlm.nih.gov/21372007/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 56.62
DMSO 71.6 202.65
DMSO:PBS (pH 7.2) (1:6) 0.1 0.28

Preparing Stock Solutions

The following data is based on the product molecular weight 353.22 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ruiz A, Alberdi E, Matute C. Mitochondrial Division Inhibitor 1 (mdivi-1) Protects Neurons against Excitotoxicity through the Modulation of Mitochondrial Function and Intracellular Ca2+ Signaling. Front Mol Neurosci. 2018 Jan 17;11:3. doi: 10.3389/fnmol.2018.00003. PMID: 29386996; PMCID: PMC5776080. 2. 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 Feb;14(2):193-204. doi: 10.1016/j.devcel.2007.11.019. PMID: 18267088; PMCID: PMC2267902. 3. Manczak M, Reddy PH. Mitochondrial division inhibitor 1 protects against mutant huntingtin-induced abnormal mitochondrial dynamics and neuronal damage in Huntington's disease. Hum Mol Genet. 2015 Dec 20;24(25):7308-25. doi: 10.1093/hmg/ddv429. Epub 2015 Oct 12. PMID: 26464486; PMCID: PMC4664169. 4. 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 Apr 27;52(5):2837-43. doi: 10.1167/iovs.09-5010. PMID: 21372007; PMCID: PMC3088566.
In vitro protocol: 1. Ruiz A, Alberdi E, Matute C. Mitochondrial Division Inhibitor 1 (mdivi-1) Protects Neurons against Excitotoxicity through the Modulation of Mitochondrial Function and Intracellular Ca2+ Signaling. Front Mol Neurosci. 2018 Jan 17;11:3. doi: 10.3389/fnmol.2018.00003. PMID: 29386996; PMCID: PMC5776080. 2. 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 Feb;14(2):193-204. doi: 10.1016/j.devcel.2007.11.019. PMID: 18267088; PMCID: PMC2267902.
In vivo protocol: 1. Manczak M, Reddy PH. Mitochondrial division inhibitor 1 protects against mutant huntingtin-induced abnormal mitochondrial dynamics and neuronal damage in Huntington's disease. Hum Mol Genet. 2015 Dec 20;24(25):7308-25. doi: 10.1093/hmg/ddv429. Epub 2015 Oct 12. PMID: 26464486; PMCID: PMC4664169. 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 Apr 27;52(5):2837-43. doi: 10.1167/iovs.09-5010. PMID: 21372007; PMCID: PMC3088566.

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1: Kanda H, Liu S, Iida T, Yi H, Huang W, Levitt RC, Lubarsky DA, Candiotti KA, Hao S. Inhibition of Mitochondrial Fission Protein Reduced Mechanical Allodynia and Suppressed Spinal Mitochondrial Superoxide Induced by Perineural Human Immunodeficiency Virus gp120 in Rats. Anesth Analg. 2015 Sep 28. [Epub ahead of print] PubMed PMID: 26418124.

2: Rakhmatullina D, Ponomareva A, Gazizova N, Minibayeva F. Mitochondrial morphology and dynamics in Triticum aestivum roots in response to rotenone and antimycin A. Protoplasma. 2015 Sep 28. [Epub ahead of print] PubMed PMID: 26411562.

3: Twaroski DM, Yan Y, Zaja I, Clark E, Bosnjak ZJ, Bai X. Altered Mitochondrial Dynamics Contributes to Propofol-induced Cell Death in Human Stem Cell-derived Neurons. Anesthesiology. 2015 Sep 9. [Epub ahead of print] PubMed PMID: 26352374.

4: Suzuki-Karasaki Y, Fujiwara K, Saito K, Suzuki-Karasaki M, Ochiai T, Soma M. Distinct effects of TRAIL on the mitochondrial network in human cancer cells and normal cells: role of plasma membrane depolarization. Oncotarget. 2015 Aug 28;6(25):21572-88. PubMed PMID: 26057632.

5: Ong SB, Kalkhoran SB, Cabrera-Fuentes HA, Hausenloy DJ. Mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease. Eur J Pharmacol. 2015 Sep 15;763(Pt A):104-14. doi: 10.1016/j.ejphar.2015.04.056. Epub 2015 May 16. PubMed PMID: 25987420.

6: Li G, Jia Z, Cao Y, Wang Y, Li H, Zhang Z, Bi J, Lv G, Fan Z. Mitochondrial Division Inhibitor 1 Ameliorates Mitochondrial Injury, Apoptosis, and Motor Dysfunction After Acute Spinal Cord Injury in Rats. Neurochem Res. 2015 Jul;40(7):1379-92. doi: 10.1007/s11064-015-1604-3. Epub 2015 May 13. PubMed PMID: 25968480.

7: Liu JM, Yi Z, Liu SZ, Chang JH, Dang XB, Li QY, Zhang YL. The mitochondrial division inhibitor mdivi-1 attenuates spinal cord ischemia-reperfusion injury both in vitro and in vivo: Involvement of BK channels. Brain Res. 2015 Sep 4;1619:155-65. doi: 10.1016/j.brainres.2015.03.033. Epub 2015 Mar 24. PubMed PMID: 25818100.

8: Sumida M, Doi K, Ogasawara E, Yamashita T, Hamasaki Y, Kariya T, Takimoto E, Yahagi N, Nangaku M, Noiri E. Regulation of Mitochondrial Dynamics by Dynamin-Related Protein-1 in Acute Cardiorenal Syndrome. J Am Soc Nephrol. 2015 Oct;26(10):2378-87. doi: 10.1681/ASN.2014080750. Epub 2015 Feb 2. PubMed PMID: 25644112.

9: Sharp WW, Beiser DG, Fang YH, Han M, Piao L, Varughese J, Archer SL. Inhibition of the mitochondrial fission protein dynamin-related protein 1 improves survival in a murine cardiac arrest model. Crit Care Med. 2015 Feb;43(2):e38-47. doi: 10.1097/CCM.0000000000000817. PubMed PMID: 25599491; PubMed Central PMCID: PMC4342059.

10: Qian W, Salamoun J, Wang J, Roginskaya V, Van Houten B, Wipf P. The combination of thioxodihydroquinazolinones and platinum drugs reverses platinum resistance in tumor cells by inducing mitochondrial apoptosis independent of Bax and Bak. Bioorg Med Chem Lett. 2015 Feb 15;25(4):856-63. doi: 10.1016/j.bmcl.2014.12.072. Epub 2014 Dec 30. PubMed PMID: 25582599; PubMed Central PMCID: PMC4318771.

11: Yeon JY, Min SH, Park HJ, Kim JW, Lee YH, Park SY, Jeong PS, Park H, Lee DS, Kim SU, Chang KT, Koo DB. Mdivi-1, mitochondrial fission inhibitor, impairs developmental competence and mitochondrial function of embryos and cells in pigs. J Reprod Dev. 2015;61(2):81-9. doi: 10.1262/jrd.2014-070. Epub 2014 Dec 12. PubMed PMID: 25501014; PubMed Central PMCID: PMC4410306.

12: Cunniff B, Wozniak AN, Sweeney P, DeCosta K, Heintz NH. Peroxiredoxin 3 levels regulate a mitochondrial redox setpoint in malignant mesothelioma cells. Redox Biol. 2014;3:79-87. doi: 10.1016/j.redox.2014.11.003. Epub 2014 Nov 18. PubMed PMID: 25462069; PubMed Central PMCID: PMC4297934.

13: Wang J, Li J, Santana-Santos L, Shuda M, Sobol RW, Van Houten B, Qian W. A novel strategy for targeted killing of tumor cells: Induction of multipolar acentrosomal mitotic spindles with a quinazolinone derivative mdivi-1. Mol Oncol. 2015 Feb;9(2):488-502. doi: 10.1016/j.molonc.2014.10.002. Epub 2014 Oct 17. PubMed PMID: 25458053; PubMed Central PMCID: PMC4305024.

14: Wang J, Hansen K, Edwards R, Van Houten B, Qian W. Mitochondrial division inhibitor 1 (mdivi-1) enhances death receptor-mediated apoptosis in human ovarian cancer cells. Biochem Biophys Res Commun. 2015 Jan 2;456(1):7-12. doi: 10.1016/j.bbrc.2014.11.010. Epub 2014 Nov 13. PubMed PMID: 25446129; PubMed Central PMCID: PMC4297922.

15: Han XJ, Yang ZJ, Jiang LP, Wei YF, Liao MF, Qian Y, Li Y, Huang X, Wang JB, Xin HB, Wan YY. Mitochondrial dynamics regulates hypoxia-induced migration and antineoplastic activity of cisplatin in breast cancer cells. Int J Oncol. 2015 Feb;46(2):691-700. doi: 10.3892/ijo.2014.2781. Epub 2014 Nov 27. PubMed PMID: 25434519.

16: Cui M, Ding H, Chen F, Zhao Y, Yang Q, Dong Q. Mdivi-1 Protects Against Ischemic Brain Injury via Elevating Extracellular Adenosine in a cAMP/CREB-CD39-Dependent Manner. Mol Neurobiol. 2014 Nov 27. [Epub ahead of print] PubMed PMID: 25428621.

17: Lim S, Lee SY, Seo HH, Ham O, Lee C, Park JH, Lee J, Seung M, Yun I, Han SM, Lee S, Choi E, Hwang KC. Regulation of mitochondrial morphology by positive feedback interaction between PKCδ and Drp1 in vascular smooth muscle cell. J Cell Biochem. 2015 Apr;116(4):648-60. doi: 10.1002/jcb.25016. PubMed PMID: 25399916.

18: Numadate A, Mita Y, Matsumoto Y, Fujii S, Hashimoto Y. Development of 2-thioxoquinazoline-4-one derivatives as dual and selective inhibitors of dynamin-related protein 1 (Drp1) and puromycin-sensitive aminopeptidase (PSA). Chem Pharm Bull (Tokyo). 2014;62(10):979-88. PubMed PMID: 25273056.

19: Akita M, Suzuki-Karasaki M, Fujiwara K, Nakagawa C, Soma M, Yoshida Y, Ochiai T, Tokuhashi Y, Suzuki-Karasaki Y. Mitochondrial division inhibitor-1 induces mitochondrial hyperfusion and sensitizes human cancer cells to TRAIL-induced apoptosis. Int J Oncol. 2014 Nov;45(5):1901-12. doi: 10.3892/ijo.2014.2608. Epub 2014 Aug 18. PubMed PMID: 25174275.

20: Mattiolo P, Barbero-Farran A, Amigó J, Ripamonti M, Ribas J, Boix J. Cell death induced by 2-phenylethynesulfonamide uncovers a pro-survival function of BAX. Cancer Lett. 2014 Nov 1;354(1):115-21. doi: 10.1016/j.canlet.2014.07.037. Epub 2014 Aug 8. PubMed PMID: 25111896.