Brefeldin A

Protein trafficking inhibitor; Inhibits Sec7-containing guanine-exchange factor (GEF)

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Protein trafficking inhibitor; Inhibits Sec7-containing guanine-exchange factor (GEF)
From: 111 USD

Overview

Brefeldin A is a fungal lactone antibiotic, produced by many species, including Eupenicillium brefeldianum (Klausner et al.). It reversibly interferes with protein trafficking and secretion mediated by the Golgi apparatus and endoplasmic reticulum by indirect inhibition of ADP-ribosylation factor (ARF; Klausner et al.; Helms & Rothman; Robinson et al.; Morinaga et al.; Moss & Vaughan; Nebenführ et al.; Ktistakis et al.). Brefeldin A binds to Sec7-containing guanine-exchange factor (GEF) at the ARF-GDP-Sec7 interface, preventing the conformational change required to release GDP and activate ARF (Mossessova et al.).

CELL LINE DEVELOPMENT
· Improves clustered regularly interspaced palindromic repeats (CRISPR)-mediated homology-directed repair (HDR) in mouse embryonic stem cells (Yu et al.).

CANCER RESEARCH
· Induces apoptosis in human leukemia (HL60, K562) and colon carcinoma (HT-29) cell lines (Shao et al.).
· Reduces survival, induces apoptosis and inhibits clonogenic activity of Colo 205 colorectal cancer stem cell line (Tseng et al.).
Alternative Names:
Ascotoxin; BFA; Cyanein; Decumbin; Nectrolide; NSC 56310; NSC 89671; NSC 107456; NSC 244390; Synergisidin
CAS Number:
20350-15-6
Chemical Formula:
C₁₆H₂₄O₄
Molecular Weight:
280.4 g/mol
Purity:
≥ 98%
Target:
GEF

Scientific Resources

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Educational Materials

(3)

Data and Publications

Publications

(11)
Cell stem cell 2015 FEB

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

Yu C et al.

Abstract

The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells.
Molecules (Basel, Switzerland) 2013

Brefeldin a effectively inhibits cancer stem cell-like properties and MMP-9 activity in human colorectal cancer Colo 205 cells.

Tseng C-N et al.

Abstract

Cancer stem cells (CSCs) are a small subset of cancer cells with indefinite potential for self-renewal and the capacity to drive tumorigenesis. Brefeldin A (BFA) is an antibiotic that is known to block protein transport and induce endoplasmic reticulum (ER) stress in eukaryotic cells, but its effects on colorectal CSCs are unknown. We investigated the inhibitory effect of BFA on human colorectal cancer Colo 205 cells. We found that BFA effectively reduced the survival of suspension Colo 205 cells (IC₅₀ = ˜15 ng/mL) by inducing apoptosis, and inhibited the clonogenic activity of Colo 205 CSCs in tumorsphere formation assay and soft agar colony formation assay in the same nanogram per milliliter range. We also discovered that at such low concentrations, BFA effectively induced endoplasmic reticulum (ER) stress response as indicated by the increased mRNA expression of ER stress-related genes, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP). Finally, we found that BFA reduced the activity of matrix metallopeptidase 9 (MMP-9). These findings suggest that BFA can effectively suppress the progression of colorectal cancer during the tumorigenesis and metastasis stages. These results may lead to the development of novel therapies for the treatment of colorectal cancer.
Plant physiology 2008 AUG

The endosomal system of plants: charting new and familiar territories.

Robinson DG et al.

Abstract

Molecular cell 2003

Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism.

Mossessova E et al.

Abstract

ARF GTPases are activated by guanine nucleotide exchange factors (GEFs) of the Sec7 family that promote the exchange of GDP for GTP. Brefeldin A (BFA) is a fungal metabolite that binds to the ARF1*GDP*Sec7 complex and blocks GEF activity at an early stage of the reaction, prior to guanine nucleotide release. The crystal structure of the ARF1*GDP*Sec7*BFA complex shows that BFA binds at the protein-protein interface to inhibit conformational changes in ARF1 required for Sec7 to dislodge the GDP molecule. Based on a comparative analysis of the inhibited complex, nucleotide-free ARF1*Sec7 and ARF1*GDP, we suggest that, in addition to forcing nucleotide release, the ARF1-Sec7 binding energy is used to open a cavity on ARF1 to facilitate the rearrangement of hydrophobic core residues between the GDP and GTP conformations. Thus, the Sec7 domain may act as a dual catalyst, facilitating both nucleotide release and conformational switching on ARF proteins.
Plant physiology 2002

Brefeldin A: deciphering an enigmatic inhibitor of secretion.

Nebenfü et al.

Abstract

STEMCELL TECHNOLOGIES INC.’S QUALITY MANAGEMENT SYSTEM IS CERTIFIED TO ISO 13485. PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED.