Exosomes are small vesicles that are released by cells into the extracellular space. They are formed by the invagination of the cell membrane and are then pinched off and released into the surrounding environment. Exosomes are typically about 30-100 nanometers in diameter and are composed of a lipid bilayer that encloses a variety of biomolecules, including proteins, RNA and lipids.

Exosomes play an important role in intercellular communication and are involved in a wide range of physiological and pathological processes. They can act as a means of transporting molecules between cells, help to modulate the immune system and regulate cell proliferation, differentiation and apoptosis. Some recent studies have found exosomes to be a potential diagnostic marker for cancer and other diseases, while others have investigated the use of exosomes as a way to deliver therapeutic molecules to specific cells or tissues.

RAS signaling directly regulates the sorting of a variety of cargos into exosomes. RAS proteins are small GTPases that play a critical role in cell signaling pathways. Farnesyltransferase (FTase) is responsible for the addition of a farnesyl group to RAS proteins, which is an essential step in their proper function and localization within the cell.

Manumycin A, a natural antibiotic, was identified as an inhibitor of exosome biogenesis and secretion. Manumycin A is a selective inhibitor of FTase. By inhibiting the farnesylation of RAS, Manumycin A suppresses RAS/RAF/ERK1/2 signaling and reduces exosome generation. Targeting exosome biogenesis might be crucial for RAS signaling inhibitors to exert their anticancer effects.

Figure: Schematic of exosome biogenesis and inhibition (adapted from M. Catalano & L. O'Discroll; J. Extracell. Vesicles 9, 1703244 (2019).

Literature References:

1. Manumycin A and Its Analogues Are Irreversible Inhibitors of Neutral Sphingomyelinase: C. Arenz, et al.; Chem. Biochem. 2, 141 (2001)

2. Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells: A. Datta, et al.; Cancer Lett. 408, 73 (2017)

3. Manumycin A Is a Potent Inhibitor of Mammalian Thioredoxin Reductase‑1 (TrxR-1): A. Tuladhar & K.S. Rein; ACS Med. Chem. Lett. 9, 318 (2018)

4. Inhibiting extracellular vesicles formation and release: a review of EV inhibitors: M. Catalano & L. O’Driscoll; J. Extracell. Vesicles 9, 1703244 (2019) (Review)

5. Role of Ceramides and Lysosomes in Extracellular Vesicle Biogenesis, Cargo Sorting and Release: R. Horbay, et al.; Int. J. Mol. Sci. 23, 15317 (2022) (Review)

6. Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer: Q.-F. Han, et al.; Mol. Cancer 21, 207 (2022) (Review)

7. Analyzing the postulated inhibitory effect of Manumycin A on farnesyltransferase: A. Hagemann, et al.; Front. Chem. 10, 967947 (2022) (Review)

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Manumycin A

Manumycin A is a potent, selective and competitive cell permeable RAS-farnesyltransferase inhibitor and an irreversible neutral sphingomyelinase nSMase inhibitor.

AG-CN2-2000 for Catalog and Bulk Items (1 mg, 5 mg, 10 mg) 

This compound has been found to have a variety of biological activities, including:

• Antimicrobial activity: Against a wide range of bacteria, including Gram-positive and Gram-negative species. It is particularly effective against methicillin-resistant Staphylococcus aureus (MRSA) and other antibiotic-resistant bacteria.
• Antitumor activity: Against a variety of cancer cell lines, including breast, ovarian and lung cancer. Works by inducing apoptosis (programmed cell death) in cancer cells and inhibiting angiogenesis in tumors.
• Anti-inflammatory activity: By inhibiting the production of pro-inflammatory molecules such as TNF-α and IL-6.
• Exosome inhibitory activity: Inhibits the formation and release of exosomes.
• Immunomodulatory activity: Modulates the immune system by upregulating the production of certain immune cells and cytokines.

AdipoGen Life Sciences is an original Manufacturer of Manumycin A. Available from stock in BULK quantities!

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STANDARD Exosomes Markers

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Sensitive and specific antibodies are an essential tool for the detection of extracellular vesicles (EVs), including exosomes, which express antigens with 3D conformations and/or post-translational modifications that often differ from the cellular counterpart. The group of tetraspanin proteins CD9, CD63 and CD81 are the most common EV-associated markers reported in the literature and have been used for EV capture in many studies, including ELISA, flow cytometry and lab-on-a-chip assays. Each of these tetraspanins has been demonstrated to play an active role in EV biogenesis or cargo sorting, suggesting their essential role in the EV secretory pathway. Ancell Corporation offers specific and sensitive antibodies for tetraspanin detection and exosome capture and a plethora of additional antigen-specific antibodies which consequently allows to phenotype EV populations based on the antigen profile.

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For a List of human CD Antibodies available through AdipoGen Life Sciences, please download the Ancell Corporation Brochure.

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