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 in different breast cancer cells a dramatic decrease in cell proliferation and survival. In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration. . Note: The correct structure for FR054 is CAS#35954-65-5 which is the 6S-isomer. Some vendors are selling wrong structure for FAR054 (the incorrect structure has CAS#10378-06-0, which is the 6R-isomer). Note this product is being supplied as ethanol solution at 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 if FR054 could hamper cell adhesion and migration in MDA-MB-231 cells by interfering with β1 integrin membrane localization. First, it was confirmed that FR054 induced a dose-dependent cell detachment not associated to cell death. Then, cell surface-active β1 integrin by confocal microscopy upon 24 h of FR054 (250 μM) was evaluated. Treated cells showed a more clustered surface staining and around 70% reduction of β1 integrin as compared with untreated ones. Analysis of β1 protein expression in whole-cell lysates indicated unchanged levels between untreated and treated cells, confirming that FR054 altered β1 membrane localization. FR054-treated cells also showed around 60% and 50% reduction in cell adhesion and migration, respectively. Altogether these results indicate that FR054 is able to reduce active β1 integrin membrane localization leading to a dramatic reduction of adhesion and migration of MDA-MB-231 cancer cells.; 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 MDA-MB-231 cells; 7 days after cells injection (tumors volume of around 180 ± 40 mm3), mice underwent intraperitoneal injection of one concentration of FR054 (1000 mg/kg) administered in single or fractionated dose (twice a day 500 mg/kg/dose) as compared to vehicle alone (10% DMSO). After 5 days of FR054 treatment, mice treated in fractionated dose showed a tumor growth stasis and a tumor volume variation significantly lower than control mice. No differences in the mice body weights and no apparent signs of morbidity based on body condition scoring were observed. The prolonged treatment with FR054 confirmed no toxic effects in mice health conditions, no body weight loss and induced a reduction of tumor growth rate (TGI = 41.77) since the percentage of volume variation was significantly smaller after the prolonged treatment than the control mice (p < 0.05). Thus, FR054 appears to have an in vivo antitumor efficacy that is higher when administered twice a day compared to 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).