A8627-1mg | Bafilomycin A1 [88899-55-2] Clinisciences

Background

Bafilomycin A1 is a selective inhibitor of vacuolar H+ ATPases (V-ATPases) with I₅₀ values of 4-400 nmol/mg ¹.

Bafilomycin A1 was treated to different types of membrane ATPases with the dependent I₅₀ of 400 nmol/mg, 4 nmol/mg and 50 nmol/mg for the vacuolar ATPases of a fungus (N. crassa), a plant (Z. mays), and an animal (bovine abrenal medulla). In addition, the inhibitory effect of bafilomycin A1 on vacuolar ATPases was further determined by testing its influence on H⁺-pumping activity. H⁺ translocation was completely inhibited by 10 nM bafilomycin A1 ¹. Other study has shown that bafilomycin A1 strongly inhibited the pit-forming activity of osteoclasts. The subcellular localization of V-ATPase in osteoclasts was been treated with or without bafilomycin A1 by immunoelectron microscopy. These results suggested that disruption of V-ATPase localization to the ruffled border by bafilomycin A1 resulted in the lack of acidification of the dentine surface ².

Notes: I₅₀ values is umol of bafilomycin AI per mg of protein giving 50% inhibition of ATPase activity.

References:
1. Bowman E J, Siebers A, Altendorf K. Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells[J]. Proceedings of the National Academy of Sciences, 1988, 85(21): 7972-7976.
2. Takami M, Suda K, Sahara T, et al. Involvement of vacuolar H+-ATPase in incorporation of risedronate into osteoclasts[J]. Bone, 2003, 32(4): 341-349.

Product Citation

1. Charlotte Nugues, Dayani Rajamanoharan, et al. "Lysosome exocytosis is required for mitosis in mammalian cells." Biochem Biophys Res Commun. 2022 Oct 20;626:211-219. PMID: 35998546
2. Yukang Wen, Zhengkun Chen, et al. "Incomplete autophagy promotes the proliferation of Mycoplasma hyopneumoniae through the JNK and Akt pathways in porcine alveolar macrophages." Vet Res. 2022 Aug 4;53(1):62. PMID: 35927699
3. Stavroula Zagkou, Valentine Marais, et al. "Design and Evaluation of Autophagy-Inducing Particles for the Treatment of Abnormal Lipid Accumulation." Pharmaceutics. 2022 Jun 29;14(7):1379. PMID: 35890275
4. Nima Nalin. "Nicotinamide mononucleotide imparts protection against Doxorubicin-induced cardiotoxicity by maintaining lysosomal acidification." The University of Western Ontario.
5. A‑Ri Cho, Hee Jung Sul, et al. "RNF43 R117fs mutant positively regulates Wnt/β-catenin signaling by failing to internalize FZD expressed on the cell surface." Sci Rep. 2022 Apr 29;12(1):7013. PMID: 35487932
6. Magdalena Delgado, Randall R. Rainwater, et al. "Primary acute lymphoblastic leukemia cells are susceptible to microtubule depolymerization in G1 and M phases through distinct cell death pathways." J Biol Chem. 2022 Jun;298(6):101939. PMID: 35436470
7. Chunhua Shu, Rui Wang, et al. "The "Dextran-Magnetic Layered Double Hydroxide-Fluorouracil" Drug Delivery System Exerts Its Anti-tumor Effect by Inducing Lysosomal Membrane Permeability in the Process of Cell Death." Biol Pharm Bull. 2021 Oct 1;44(10):1473-1483. PMID: 34305072
8. Zining Wang, Feifei Xu, et al. "Modulation of lactate-lysosome axis in dendritic cells by clotrimazole potentiates antitumor immunity." J Immunother Cancer. 2021 May;9(5):e002155. PMID: 34016722
9. Huiting Jia, Xindong Wang, et al. "Zinc(II)-Dipicolylamine Analogs Mediated PEI1.8k/pDNA Vector: Effect of Ligand Structure on the Gene Transport Process." Macromol Biosci. 2021 Jun;21(6):e2100048. PMID: 33861507
10. Zhuo Sun, Yidan Cao, et al. "Antiangiogenic effect of arsenic trioxide in HUVECs by FoxO3a‐regulated autophagy." J Biochem Mol Toxicol. 2021 Feb 16;e22728. PMID: 33592126
11. Wei Lei, Zhenyun Huo, et al. "Jervine inhibits non-small cell lung cancer (NSCLC) progression by suppressing Hedgehog and AKT signaling via triggering autophagy-regulated apoptosis." Biochem Biophys Res Commun. 2020 Dec 10;533(3):397-403. PMID: 32972750
12. Peng, Tianqing. "Nicotinamide mononucleotide imparts protection against Doxorubicin-induced cardiotoxicity by maintaining lysosomal acidification." Western University, 8-4-2020.
13. Xie X, Yang C, et al. "Advanced glycation end products reduce macrophage-mediated killing of Staphylococcus aureus by ARL8 upregulation and inhibition of autolysosome formation." Eur J Immunol. 2020;10.1002/eji.201948477. PMID: 32250445
14. Wu L, Duan Q, et al. "Zearalenone Blocks Autophagy Flow and Induces Cell Apoptosis During Embryo Implantation in Gilts." Toxicol Sci. 2020;175(1):126-139. PMID: 32239165
15. Lin Tang, Xinxun Xiao, et al. "Induction of oocyte maturation and changes in the biochemical composition, physiology and molecular biology of oocytes during maturation and hydration in the orange-spotted grouper (Epinephelus coioides)." aquaculture 4 December 2019. PII: S0044-8486(19)33325-3.
16. Liang D, Wang HY, et al. "W941, a new PI3K inhibitor, exhibits preferable anti-proliferative activities against nonsmall cell lung cancer with autophagy inhibitors." Invest New Drugs. 2019 Dec 10. PMID: 31823159
17. Xinchun Li, Li Zhong, et al. "Phosphorylation of IRS4 by CK1γ2 promotes its degradation by CHIP through the ubiquitin/lysosome pathway" Theranostics, 2018, Vol. 8, Issue13.
18. Wang H, Liu W, et al. "Inhibitor analysis revealed that clathrin-mediated endocytosis is involed in cellular entry of type III grass carp reovirus." Virol J. 2018 May 24;15(1):92. PMID: 29793525
19. Boyd Tressler, Andrea Michelle. "Mechanisms of Extracellular Nucleotide Accumulation During Regulated Cell Death in Tumor Cells." rave.ohiolink.edu, May 2016.
20. Liu, Shuangxin, et al. "Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R." International journal of molecular medicine (2015). PMID: 26647715
21. Boyd-Tressler, Andrea, et al. "Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-Independent Mechanism." Journal of Biological Chemistry (2014): jbc-M114. PMID: 25112874

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Chemical Properties

Physical Appearance	A crystalline solid
Storage	Desiccate at -20°C
M.Wt	622.84
Cas No.	88899-55-2
Formula	C₃₅H₅₈O₉
Solubility	Soluble in DMSO
Chemical Name	(3Z,5E,7R,8S,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-4-[(2R,4R,5S,6R)-2,4-dihydroxy-5-methyl-6-propan-2-yloxan-2-yl]-3-hydroxypentan-2-yl]-8-hydroxy-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraen-2-one
SDF	Download SDF
Canonical SMILES	CC1CC(=CC=CC(C(OC(=O)C(=CC(=CC(C1O)C)C)OC)C(C)C(C(C)C2(CC(C(C(O2)C(C)C)C)O)O)O)OC)C
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.

Protocol

Cell experiment [1]:
Cell lines	HeLa cells
Preparation method	The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	0 ~ 20 nM
Applications	Bafilomycin A1 dose-dependently inhibited the vacuolization of Hela cells induced by H. pylori, showing a 50% effect at 4 nM and a complete inhibition at 12.5 nM. In addition, Bafilomycin A1 also efficiently restored vacuolated cells to a normal appearance.
Animal experiment [2]:
Animal models	Young freshwater tilapias
Dosage form	0 ~ 10-5 mol/L; 30 mins
Applications	In young tilapias, Bafilomycin A1 dose-dependently inhibited the rate of Na+ uptake with a Ki value of 1.6 × 10-7 mol/L. The inhibitory effect (20%) was observed at a concentration as low as 10-8 mol/L and increased linearly up to a concentration of 10-6 mol/L, after which it remained at approximately 90 % inhibition.
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]. Papini E, Bugnoli M, De Bernard M, Figura N, Rappuoli R, Montecucco C. Bafilomycin A1 inhibits Helicobacter pylori-induced vacuolization of HeLa cells. Mol Microbiol. 1993 Jan;7(2):323-7. [2]. Fenwick JC, Wendelaar Bonga SE, Flik G. In vivo bafilomycin-sensitive Na(+) uptake in young freshwater fish. J Exp Biol. 1999 Dec;202 Pt 24:3659-66.

Biological Activity

Description	Bafilomycin A1 is a selective and reversible inhibitor of vacuolar H+ ATPases (V-ATPases) with IC50 value of 4-400 nM.
Targets	V-ATPases
IC50	4-400 nM