Vacuolin-1 | CAS#351986-85-1 | lysosome fusion inhibitor

MedKoo Cat#: 562795 | Name: Vacuolin-1

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Vacuolin-1 is a cell-permeable inhibitor of Ca2+ dependent fusion of lysosomes to the cell membrane. It acts by inhibiting release of lysosomal content. Vacuolin-1 is also a potent and selective PIKfyve inhibitor, and inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition.

Chemical Structure

Vacuolin-1

CAS#351986-85-1

Theoretical Analysis

MedKoo Cat#: 562795

Name: Vacuolin-1

CAS#: 351986-85-1

Chemical Formula: C26H24IN7O

Exact Mass: 577.1087

Molecular Weight: 577.43

Elemental Analysis: C, 54.08; H, 4.19; I, 21.98; N, 16.98; O, 2.77

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,750.00	Ready to ship
2g	USD 6,250.00	2 Weeks

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Synonym

Vacuolin-1; Vacuolin 1; Vacuolin1;

IUPAC/Chemical Name

3-Iodobenzaldehyde [4-(diphenylamino)-6-(4-morpholinyl)-1,3,5-triazin-2-yl]hydrazone

InChi Key

JMEJTSRAQUFNOP-TURZUDJPSA-N

InChi Code

InChI=1S/C26H24IN7O/c27-21-9-7-8-20(18-21)19-28-32-24-29-25(33-14-16-35-17-15-33)31-26(30-24)34(22-10-3-1-4-11-22)23-12-5-2-6-13-23/h1-13,18-19H,14-17H2,(H,29,30,31,32)/b28-19+

SMILES Code

IC1=CC(/C=N/NC2=NC(N(C3=CC=CC=C3)C4=CC=CC=C4)=NC(N5CCOCC5)=N2)=CC=C1

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

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R11B24

QC Data

View QC data: current batch, Lot#C20R11B24

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Vacuolin-1 is a potent and cell-permeable lysosomal exocytosis inhibitor.

In vitro activity:

One molecule, vacuolin-1, potently induced LC3B yellow puncta, not red only puncta (Fig. 1A; Fig. S1). Western blot analyses further confirmed that lipidated LC3B-II was markedly increased in cells treated with vacuolin-1. SQSTM1/p62, an autophagic substrate, was also accumulated in cells treated with vacuolin-1, suggesting that vacuolin-1 inhibits the fusion between autophagosome and lysosomes (Fig. 1B). Indeed, GFP-LC3B puncta were greatly increased in vacuolin-1 treated cells and did not colocalize with lysosome-associated membrane protein 1 (LAMP1) (Fig. 1C), which was similar to the cells treated with BAF (Fig. S2). Reference: Autophagy. 2014 Nov; 10(11): 1895–1905. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502727/

In vivo activity:

This study showed that V1 (vacuolin-1) treatment (oral delivery of 15 mg/kg or 30 mg/kg per day) significantly decreased the number of tumor nodules in the lungs (Fig.3A, B), the number of the mammary bearing tumor (Fig. 3C), and the weight of mammary tumors in a concentration-dependent manner (Fig. 3D). Similar results have been observed following intraperitoneal (IP) delivery of V1 (20 mg/kg, daily) in this transgenic mouse model (Fig. S3A–D). Taken together, these results demonstrate that V1 potently inhibits both tumor growth and metastasis of mouse MMTV-PyMT mammary carcinoma. Reference: Oncogene. 2021; 40(10): 1775–1791. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946642/

	Solvent	mg/mL	mM
Solubility
	DMSO	18.3	31.74
	DMSO:PBS (pH 7.2) (1:7)	0.1	0.21
	DMF	3.0	5.20

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 577.43 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.

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. Sano O, Kazetani K, Funata M, Fukuda Y, Matsui J, Iwata H. Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition. FEBS Lett. 2016 Jun;590(11):1576-85. doi: 10.1002/1873-3468.12195. Epub 2016 May 13. PMID: 27135648. 2. Lu Y, Dong S, Hao B, Li C, Zhu K, Guo W, Wang Q, Cheung KH, Wong CW, Wu WT, Markus H, Yue J. Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A. Autophagy. 2014;10(11):1895-905. doi: 10.4161/auto.32200. Epub 2014 Oct 30. Erratum in: Autophagy. 2018;14 (1):176-177. PMID: 25483964; PMCID: PMC4502727. 3. Ye Z, Wang D, Lu Y, He Y, Yu J, Wei W, Chen C, Wang R, Zhang L, Zhang L, Le MTN, Cho WC, Yang M, Zhang H, Yue J. Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ. Oncogene. 2021 Mar;40(10):1775-1791. doi: 10.1038/s41388-021-01662-3. Epub 2021 Feb 9. PMID: 33564074; PMCID: PMC7946642.

In vitro protocol:

In vivo protocol:

1. Ye Z, Wang D, Lu Y, He Y, Yu J, Wei W, Chen C, Wang R, Zhang L, Zhang L, Le MTN, Cho WC, Yang M, Zhang H, Yue J. Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ. Oncogene. 2021 Mar;40(10):1775-1791. doi: 10.1038/s41388-021-01662-3. Epub 2021 Feb 9. PMID: 33564074; PMCID: PMC7946642.

1: Vacuolin-1 potently and reversibly inhibits autophagy by activating Rab5. Autophagy. 2018;14(1):176-177. doi: 10.1080/15548627.2017.1367474. Epub 2018 Feb 1. PubMed PMID: 29388871; PubMed Central PMCID: PMC5846563. 2: Layhadi JA, Fountain SJ. P2X4 Receptor-Dependent Ca(2+) Influx in Model Human Monocytes and Macrophages. Int J Mol Sci. 2017 Oct 27;18(11). pii: E2261. doi: 10.3390/ijms18112261. PubMed PMID: 29077063; PubMed Central PMCID: PMC5713231. 3: Jiang LQ, Wang TY, Webster TJ, Duan HJ, Qiu JY, Zhao ZM, Yin XX, Zheng CL. Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport. Int J Nanomedicine. 2017 Aug 31;12:6383-6398. doi: 10.2147/IJN.S142060. eCollection 2017. PubMed PMID: 28919742; PubMed Central PMCID: PMC5587219. 4: Li Z, Mbah NE, Maltese WA. Vacuole-inducing compounds that disrupt endolysosomal trafficking stimulate production of exosomes by glioblastoma cells. Mol Cell Biochem. 2018 Feb;439(1-2):1-9. doi: 10.1007/s11010-017-3130-x. Epub 2017 Aug 2. PubMed PMID: 28770472; PubMed Central PMCID: PMC5796851. 5: Chen C, Lu Y, Siu HM, Guan J, Zhu L, Zhang S, Yue J, Zhang L. Identification of Novel Vacuolin-1 Analogues as Autophagy Inhibitors by Virtual Drug Screening and Chemical Synthesis. Molecules. 2017 May 27;22(6). pii: E891. doi: 10.3390/molecules22060891. PubMed PMID: 28555021. 6: Cao Q, Yang Y, Zhong XZ, Dong XP. The lysosomal Ca(2+) release channel TRPML1 regulates lysosome size by activating calmodulin. J Biol Chem. 2017 May 19;292(20):8424-8435. doi: 10.1074/jbc.M116.772160. Epub 2017 Mar 30. PubMed PMID: 28360104; PubMed Central PMCID: PMC5437247. 7: Fekri F, Delos Santos RC, Karshafian R, Antonescu CN. Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms. PLoS One. 2016 Jun 8;11(6):e0156754. doi: 10.1371/journal.pone.0156754. eCollection 2016. PubMed PMID: 27275866; PubMed Central PMCID: PMC4898768. 8: Sano O, Kazetani K, Funata M, Fukuda Y, Matsui J, Iwata H. Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition. FEBS Lett. 2016 Jun;590(11):1576-85. doi: 10.1002/1873-3468.12195. Epub 2016 May 13. PubMed PMID: 27135648. 9: Zou J, Hu B, Arpag S, Yan Q, Hamilton A, Zeng YS, Vanoye CG, Li J. Reactivation of Lysosomal Ca2+ Efflux Rescues Abnormal Lysosomal Storage in FIG4-Deficient Cells. J Neurosci. 2015 Apr 29;35(17):6801-12. doi: 10.1523/JNEUROSCI.4442-14.2015. PubMed PMID: 25926456; PubMed Central PMCID: PMC4412898. 10: Lu Y, Dong S, Hao B, Li C, Zhu K, Guo W, Wang Q, Cheung KH, Wong CW, Wu WT, Markus H, Yue J. Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A. Autophagy. 2014;10(11):1895-905. doi: 10.4161/auto.32200. Epub 2014 Oct 30. Erratum in: Autophagy. 2018;14 (1):176-177. PubMed PMID: 25483964; PubMed Central PMCID: PMC4502727. 11: Kypri E, Falkenstein K, De Lozanne A. Antagonistic control of lysosomal fusion by Rab14 and the Lyst-related protein LvsB. Traffic. 2013 May;14(5):599-609. doi: 10.1111/tra.12058. Epub 2013 Mar 12. PubMed PMID: 23387437; PubMed Central PMCID: PMC3622840. 12: Jung J, Shin YH, Konishi H, Lee SJ, Kiyama H. Possible ATP release through lysosomal exocytosis from primary sensory neurons. Biochem Biophys Res Commun. 2013 Jan 11;430(2):488-93. doi: 10.1016/j.bbrc.2012.12.009. Epub 2012 Dec 10. PubMed PMID: 23237805. 13: Shin YH, Lee SJ, Jung J. Secretion of ATP from Schwann cells through lysosomal exocytosis during Wallerian degeneration. Biochem Biophys Res Commun. 2012 Dec 14;429(3-4):163-7. doi: 10.1016/j.bbrc.2012.10.121. Epub 2012 Nov 7. PubMed PMID: 23142593. 14: Liu Y, Zhou Y, Zhu K. Inhibition of glioma cell lysosome exocytosis inhibits glioma invasion. PLoS One. 2012;7(9):e45910. doi: 10.1371/journal.pone.0045910. Epub 2012 Sep 28. PubMed PMID: 23029308; PubMed Central PMCID: PMC3461042. 15: Miller ME, Adhikary S, Kolokoltsov AA, Davey RA. Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection. J Virol. 2012 Jul;86(14):7473-83. doi: 10.1128/JVI.00136-12. Epub 2012 May 9. PubMed PMID: 22573858; PubMed Central PMCID: PMC3416309. 16: Keerthivasan G, Liu H, Gump JM, Dowdy SF, Wickrema A, Crispino JD. A novel role for survivin in erythroblast enucleation. Haematologica. 2012 Oct;97(10):1471-9. doi: 10.3324/haematol.2011.061093. Epub 2012 Apr 4. PubMed PMID: 22491741; PubMed Central PMCID: PMC3487547. 17: Durchfort N, Verhoef S, Vaughn MB, Shrestha R, Adam D, Kaplan J, Ward DM. The enlarged lysosomes in beige j cells result from decreased lysosome fission and not increased lysosome fusion. Traffic. 2012 Jan;13(1):108-19. doi: 10.1111/j.1600-0854.2011.01300.x. Epub 2011 Nov 9. PubMed PMID: 21985295; PubMed Central PMCID: PMC3237799. 18: Keerthivasan G, Small S, Liu H, Wickrema A, Crispino JD. Vesicle trafficking plays a novel role in erythroblast enucleation. Blood. 2010 Oct 28;116(17):3331-40. doi: 10.1182/blood-2010-03-277426. Epub 2010 Jul 19. PubMed PMID: 20644112; PubMed Central PMCID: PMC2995360. 19: Bao JX, Xia M, Poklis JL, Han WQ, Brimson C, Li PL. Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H992-H1002. doi: 10.1152/ajpheart.00958.2009. Epub 2010 Jan 8. PubMed PMID: 20061541; PubMed Central PMCID: PMC2838547. 20: Shaik GM, Dráberová L, Heneberg P, Dráber P. Vacuolin-1-modulated exocytosis and cell resealing in mast cells. Cell Signal. 2009 Aug;21(8):1337-45. doi: 10.1016/j.cellsig.2009.04.001. Epub 2009 Apr 17. PubMed PMID: 19376224.