FR054

• CAS: 35954-65-5
• Catalog Number: ACM35954655-1
• Category: Inhibitors
• Molecular Weight: 329.31
• Molecular Formula: C14H19NO8
• Description: FR054 is an inhibitor of the Hexosamine Biosynthetic Pathway (HBP) enzyme PGM3, with a remarkable anti-breast cancer effect. FR054 induces a significant decrease in cell proliferation and survival across various breast cancer cell lines. Notably, in a model of Triple Negative Breast Cancer (TNBC) cells, these effects are associated with FR054-dependent reductions in both N- and O-glycosylation levels, which also lead to a marked decrease in cancer cell adhesion and migration.; Note: The correct structure for FR054 is CAS#35954-65-5, which corresponds to the 6S-isomer. Some vendors may be selling an incorrect structure for FR054, identified by CAS#10378-06-0, which represents the 6R-isomer. This product is supplied as an ethanol solution at a concentration of 100mg/mL.
• Synonyms: FR054; FR-054; FR 054
• IUPAC 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)-
• Canonical SMILES: CC1=N[C@@]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O2)([H])[C@@]2([H])O1
• InChI: 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
• InChI Key: WZFQZRLQMXZMJA-KSTCHIGDSA-N
• Solubility: To be determined
• Appearance: Viscouse waxy semi-solid
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 35954-65-5 (6S-isomer); 10378-06-0 (6R-isomer)
• Biological Target: FR054 is an inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
• Drug Formulation: To be determined
• Elemental Analysis: C, 51.06; H, 5.82; N, 4.25; O, 38.87
• Exact Mass: 329.1111
• HS Tariff Code: 2934.99.03.00
• In Vitro Activity: It was tested whether FR054 could impede cell adhesion and migration by interfering with β1 integrin membrane localization. First, it was confirmed that FR054 induced a dose-dependent cell detachment that was not associated with cell death. Next, cell surface-active β1 integrin was assessed by confocal microscopy after 24 h of FR054 (250 μM) treatment. Treated cells exhibited more clustered surface staining and a ~70% reduction of β1 integrin compared to untreated cells. Analysis of β1 protein expression in whole-cell lysates showed no significant changes between untreated and treated cells, confirming that FR054 altered β1 membrane localization. Furthermore, FR054-treated cells demonstrated approximately 60% and 50% reductions in cell adhesion and migration, respectively. These results suggest that FR054 reduces active β1 integrin membrane localization, leading to a substantial reduction in cell adhesion and migration.; Reference: Cell Death Dis. 2018 Mar 7;9(3):377. https://pubmed.ncbi.nlm.nih.gov/29515119/
• In Vivo Activity: Mice were subcutaneously injected with tumor cells, and 7 days after the injection (with tumor volumes of around 180 ± 40 mm³), mice underwent intraperitoneal injection of one concentration of FR054 (1000 mg/kg), administered in a single dose or fractionated doses (twice a day, 500 mg/kg per dose), compared to vehicle alone (10% DMSO). After 5 days of FR054 treatment, mice treated with the fractionated dose showed tumor growth stasis, with tumor volume variation significantly lower than that of control mice. No differences in body weight or apparent signs of morbidity, as assessed by body condition scoring, were observed. Prolonged treatment with FR054 confirmed no toxic effects on mice health, no body weight loss, and a reduction in tumor growth rate (TGI = 41.77), as the percentage of volume variation was significantly smaller after prolonged treatment compared to control mice (p < 0.05). Thus, FR054 appears to have in vivo antitumor efficacy that is enhanced when administered twice a day compared to a single administration.; Reference: Cell Death Dis. 2018 Mar 7;9(3):377. https://pubmed.ncbi.nlm.nih.gov/29515119/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).