生物活性

• 靶点	ATPase IC50:0.2μM

• 描述Brefeldin A is a fungal lactone antibiotic produced by Penicillium brefeldianum usually used as a protein trafficking/secretion inhibitor in mammalian and other eukaryotic cells, without significant effect on protein synthesis. The main target of Brefeldin A may be Arf1, which is important to formation of protein transport vesicles^[1][2][3]. Brefeldin A could induce the rapid redistribution of the ll0-kD protein and the movement of Golgi membrane into the ER within 15min at 2μg/ml in semipermeable cells^[4]. Brefeldin A could induce a wide variety of human cancer cells to differentiation and apoptosis. It exhibited cytotoxicity to HCT 116 cells with IC50 value of 0.2μM, as well as induced DNA fragmentation and apoptotic morphological changes with IC50 values of 0.11 and 0.36 μM, respectively^[5]. Brefeldin A combined with L755507 could improve the HDR efficiency, and exhibit enhanced insertion efficiency by 2-fold, with maximal effect at 0.1 μM^[6].
• 作用机制Brefeldin A inhibits protein trafficking and secretion by interfering with the function of the Golgi apparatus, which may due to the disruption of transport vesicle formation dependent on the assembly of the COPI coat by Arf1-GTP.^[1][2][3]
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  3T3-L1	5 μg/ml	Function Assay	30 min	mimics the effects of insulin and causes robust phosphorylation of Akt (Ser 473) and phosphorylation of AS160 (Thr 642 and Ser 588)	24843827
  3T3-L1	5 μg/ml	Function Assay	30 min	recapitulates insulin action with respect to regulating Akt activity and AS160 phosphorylation	24843827
  3T3-L1	5 μg/ml	Function Assay	30 min	causes reversible redistribution of GLUT4	24843827

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• 动物研究
  剂量	Mice: 26.3 mg/kg[7] (i.v.), LD50 = 250 mg/kg[8] (i.p.)
  给药途径	i.v., i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01742364	-	-	Completed	-	-
  NCT01742364	Tuberculosis	Not Applicable	Completed	-	South Africa ... more >> SATVI, University of Cape Town Cape Town, South Africa, 7925 Collapse <<
  NCT03044509	-	-	Recruiting	December 2019	Switzerland ... more >> Kantonspital Aarau Recruiting Aarau, Switzerland, 5001 Contact: Sara Bernhard-Stirnemann, Dr med    +41628384192    sara.bernhard@ksa.ch    Kinderspital Basel Recruiting Basel, Switzerland, 4031 Contact: Marina Beaufils-Hugot, PhD    +41617042953    marina.beaufils-hugot@ukbb.ch    Contact: Noemi Meier, Master    +41617042947    noemi.meier@ukbb.ch    Principal Investigator: Nicole Ritz, PD Dr med          Sub-Investigator: Ines Mack, Dr med          Sub-Investigator: Anja Jochmann, Dr med          Sub-Investigator: Daniel Trachsel, PD Dr med          Ospedale Regionale di Bellinzona Recruiting Bellinzona, Switzerland, 6500 Contact: Lisa Kottanattu, Dr med    +41918118538    lisa.kottanattu@eoc.ch    Inselspital Bern Recruiting Bern, Switzerland, 3010 Contact: Andrea Duppenthaler, Dr. med.    +41316329414    andrea.duppenthaler@insel.ch    Hôpital des enfants - HUG Recruiting Genève, Switzerland, 1205 Contact: Anne Mornand, Dr. med.    +41223724579    anne.mornand@hcuge.ch    Sub-Investigator: Marie Rohr, Dr. med.          Kinserspital Luzern Recruiting Luzern, Switzerland, 6016 Contact: Michael Buettcher, Dr med    +41412056657    michael.buettcher@luks.ch    Kinderspital St Gallen Recruiting St. Gallen, Switzerland, 9006 Contact: Jürg Barben, Prof Dr med    +41712437111    juerg.barben@kispisg.ch    Sub-Investigator: Christian Kahlert, Dr med          Kinderklinik Zürich Recruiting Zürich, Switzerland, 8032 Contact: Christoph Berger, Prof Dr med    +41442667840    christoph.berger@kispi.uzh.ch    Sub-Investigator: Christa Relly, Dr med Collapse <<

• 参考文献

• [1] Donaldson JG, Finazzi D, et al. Brefeldin A inhibits Golgi membrane-catalysed exchange of guanine nucleotide onto ARF protein. Nature. 1992 Nov 26;360(6402):350-2.

  [2] Orci L, Tagaya M, et al. Brefeldin A, a drug that blocks secretion, prevents the assembly of non-clathrin-coated buds on Golgi cisternae. Cell. 1991 Mar 22;64(6):1183-95.

  [3] Donaldson JG, Lippincott-Schwartz J, et al. Guanine nucleotides modulate the effects of brefeldin A in semipermeable cells: regulation of the association of a 110-kD peripheral membrane protein with the Golgi apparatus. J Cell Biol. 1991 Feb;112(4):579-88.

  [4] Donaldson JG, Lippincott-Schwartz J, et al. Guanine nucleotides modulate the effects of brefeldin A in semipermeable cells: regulation of the association of a 110-kD peripheral membrane protein with the Golgi apparatus. J Cell Biol. 1991 Feb;112(4):579-88.

  [5] Zhu JW, Nagasawa H, et al. Elucidation of strict structural requirements of brefeldin A as an inducer of differentiation and apoptosis. Bioorg Med Chem. 2000 Feb;8(2):455-63.

  [6] Yu C, Liu Y, et al. Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell. 2015 Feb 5;16(2):142-7.

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