Golgicide A (GCA), a quinoline compound, is a cell-permeable, potent and rapidly reversible inhibitor of GBF1, which is one of the guanine nucleotide exchange factors (ArfGEFs). It is also an inhibitor of shiga toxin cytotoxicity. Golgicide A inhibits the effect of shiga toxin on protein synthesis with an IC50 of 3.3 μM in Vero cells. Immunofluoresence experiments demonstrates that Golgicide A causes complete dispersal of the medial-Golgi markers giantin and the cis-Golgi marker GM130 and results in a rapid redistribution of COPI from the Golgi.

Physicochemical Properties

Molecular Formula	C17H14F2N2
Molecular Weight	284.310
Exact Mass	284.113
Elemental Analysis	C, 71.82; H, 4.96; F, 13.36; N, 9.85
CAS #	1139889-93-2
Related CAS #	Golgicide A-2;1394285-50-7;Golgicide A-1;1394285-49-4;(Rac)-Golgicide A;1005036-73-6
PubChem CID	25113626
Appearance	White to off-white solid powder
LogP	4.324
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	21
Complexity	414
Defined Atom Stereocenter Count	2
SMILES	C1C=CC2C1C(NC3=C2C=C(C=C3F)F)C4=CN=CC=C4
InChi Key	NJZHEQOUHLZCOX-FTLRAWMYSA-N
InChi Code	InChI=1S/C17H14F2N2/c18-11-7-14-12-4-1-5-13(12)16(10-3-2-6-20-9-10)21-17(14)15(19)8-11/h1-4,6-9,12-13,16,21H,5H2/t12-,13+,16?/m0/s1
Chemical Name	(3aR,9bS)-6,8-difluoro-4-(pyridin-3-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline
Synonyms	Golgicide A; GCA
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	GBF1
ln Vitro	Golgicide A inhibits the effect of shiga toxin on protein synthesis with an IC50 of 3.3 μM. Golgicide A causes a decrease in GBF1-mediated Arf1 activation, arrests secretion of soluble and membrane-anchored proteins and then impairs retrograde toxin transport. Golgicide A decreases HCV RNA levels in FLRP1 cells and J6/JFH1 cells. In addition, Golgicide A causes redistribution of NS5A and accumulation of infectious viral particles in J6/JFH1 cells.
ln Vivo	N/A
Cell Assay	Golgicide A inhibits the effect of shiga toxin on protein synthesis with an IC50 of 3.3 μM in Vero cells. Immunofluoresence experiments demonstrates that Golgicide A causes complete dispersal of the medial-Golgi markers giantin and the cis-Golgi marker GM130 and results in a rapid redistribution of COPI from the Golgi. Also, Golgicide A causes a decrease in GBF1-mediated Arf1 activation, impairs retrograde toxin transport and arrests secretion of soluble and membrane-anchored proteins. Golgicide A decreases HCV RNA levels and causes redistribution of NS5A in FLRP1 cells and J6/JFH1 cells. In addition, Golgicide A causes accumulation of infectious viral particles in J6/JFH1 cells.
Animal Protocol	N/A N/A
References	[1]. Nat Chem Biol.2009 Mar;5(3):157-65) [2]. J Virol.2011 Jan;85(2):946-56. [3]. Nat Chem Biol. 2009 Mar;5(3):157-65. [4]. J Virol. 2010 Aug;84(15):7535-42.
Additional Infomation	Golgicide A is a diastereoisomeric mixture comprising racemic cis- and racemic trans-goglioside A in a 10:1 ratio. It is a potent and rapidly reversible GBF1 (Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1) inhibitor. The (3aS,4R,9bR) isomer is the most active (see Bioorg. Med. Chem. Lett., 2012, 22, 5177-5181). It has a role as a cis-Golgi ArfGEF GBF inhibitor. It contains a cis-golgicide A and a trans-golgicide A.

Solubility Data

Solubility (In Vitro)

DMSO : 57~100 mg/mL ( 200.49~351.74 mM ) Ethanol : 4 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 10% DMSO+90% (20% SBE-β-CD in Saline): ≥ 2.5 mg/mL (8.79 mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5173 mL	17.5864 mL	35.1729 mL
	5 mM	0.7035 mL	3.5173 mL	7.0346 mL
	10 mM	0.3517 mL	1.7586 mL	3.5173 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.