FR054 is an inhibitor (blocker/antagonist) of the hexosamine biosynthetic pathway (HBP) enzyme PGM3 and has significant anti-breast cancer effects. FR054 causes a dramatic decrease in cell proliferation/growth and survival in different breast cancer cells. In particular, in the triple-negative breast cancer (TNBC) cell model MDA-MB-231, these effects were associated with a reduction in FR054-dependent N- and O-glycosylation levels, which also resulted in a strong reduction in cancer cell adhesion and migration. . . Note: The correct structure of FR054 is CAS#35954-65-5, which is the 6S isomer. Some suppliers sell FAR054 with the wrong structure (wrong structure of CAS#10378-06-0, the 6R isomer). Please note that this product is supplied as a 100 mg/mL ethanol solution.

Physicochemical Properties

Molecular Formula	C14H19NO8
Molecular Weight	329.31
Exact Mass	329.111
Elemental Analysis	C, 51.06; H, 5.82; N, 4.25; O, 38.87
CAS #	35954-65-5
Related CAS #	(6R)-FR054;10378-06-0
PubChem CID	9883925
Appearance	Colorless to light yellow Viscouse waxy semi-solid
Density	1.45±0.1 g/cm3(Predicted)
Boiling Point	416.7±45.0 °C(Predicted)
LogP	-0.5
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	7
Heavy Atom Count	23
Complexity	531
Defined Atom Stereocenter Count	5
SMILES	CC1=NC2C(C(C(OC2O1)COC(=O)C)OC(=O)C)OC(=O)C
InChi Key	WZFQZRLQMXZMJA-KSTCHIGDSA-N
InChi Code	InChI=1S/C14H19NO8/c1-6-15-11-13(22-9(4)18)12(21-8(3)17)10(5-19-7(2)16)23-14(11)20-6/h10-14H,5H2,1-4H3/t10-,11-,12-,13-,14+/m1/s1
Chemical Name	5H-Pyrano[3,2-d]oxazole-6,7-diol, 5-[(acetyloxy)methyl]-3a,6,7,7a-tetrahydro-2-methyl-, diacetate (ester), (3aR,5R,6S,7R,7aR)-
Synonyms	FR054; FR-054; FR 054
HS Tariff Code	2934.99.03.00
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

ln Vitro	In breast cancer cells, FR054 (0.5–1 mM, 24-48 h) causes an early rise in proliferation, which is followed by a notable decrease in cell viability and an induction of cell display. FR054 inhibits PGM3 instead of having other unintended consequences [1]. (250 μM, 24 hours) therapy has a significant impact on MDA-MB-231 cells' levels of N- and O-glycosylation [1]. ROS-dependent cells and endoplasmic reticulum (ER) mesenchymal cells are induced in cells by FR054 [1].
ln Vivo	FR054 (1000 mg/kg, intraperitoneal injection) inhibits cancer growth in MDA-MB-231 xenograft mice [1].
Cell Assay	Cell viability assay [1] Cell Types: MDA-MB-231 cells. Tested Concentrations: 0.5-1 mM. Incubation Duration: 48 hrs (hours). Experimental Results: Viability was diminished and apoptosis was Dramatically increased compared to control clones.
Animal Protocol	Animal/Disease Models: Mice are injected subcutaneously (sc) (sc) with MDA-MB-231 cells [1]. Doses: 1000 mg/kg. Route of Administration: IP, single or divided doses (500 mg/kg/dose twice (two times) daily). Experimental Results: Twice-daily dosing appeared to have greater in vivo antitumor efficacy compared with single dosing.
References	[1]. Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis. Cell Death Dis. 2018 Mar 7;9(3):377.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~303.67 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.59 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0367 mL	15.1833 mL	30.3665 mL
	5 mM	0.6073 mL	3.0367 mL	6.0733 mL
	10 mM	0.3037 mL	1.5183 mL	3.0367 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.