Regorafenib monohydrate, Inhibitor

Regorafenib monohydrate

Cat. Num. AAA5755754

• Purity: 98.00%
• Synonyms: Regorafenib monohydrate; inhibitor

• Purity/Purification: 98.00%
• Form/Format: Solid. Powder

• Solubility: DMSO: 49mg/mL (97.84mM); (<1mg/ml refers to the product slightly soluble or insoluble)
• Formula: C21H17ClF4N4O4
• SMILES: O.CNC(=O)c1cc(Oc2ccc(NC(=O)Nc3ccc(Cl)c(c3)C(F)(F)F)c(F)c2)ccn1
• CAS Number: 1019206-88-2
• Cell Research: Each cell line was seeded at 0.3x10^5 cells/2ml of DMEM containing 10% FBS in 35mM tissue culture dishes. The cells were incubated for 24 hours to allow attachment, and then the medium was replaced by fresh culture medium containing Regorafenib at increasing concentrations (1uM, 2.5uM, 5uM, 7.5uM and 10uM). In these experimental conditions, the cells were allowed to grow for 72 or 96 hours. Time-course experiments on Hep3B cells were performed with 7.5uM of Regorafenib at short (15, 60, 180 minutes.), middle (24, 48, 72 and 96 h) or long times (up to seven days). When the cells were treated for long times the drug was replaced with a fresh one. Each experiment included a control with the equivalent concentration of DMSO (solvent control) as the one used for adding Regorafenib. Each experiment was performed in triplicate and repeated 3 times. Subsequent analyses were performed at specific Regorafenib concentrations and incubation times [2]. Cell lines:
• Kinase Assay: In vitro assays using recombinant VEGFR2 (murine aa785-aa1367), VEGFR3 (murine aa818-aa1363), PDGFR-b (aa561-aa1106), RAF-1 (aa305-aa648) and BRAFV600E (aa409-aa765) kinase domains were performed as previously described. Initial in vitro kinase inhibition profiling was performed at a fixed 1uM compound concentration under Millipore standard conditions [10uM adenosine-50'- triphosphate (ATP) concentration]. Inhibitory concentration of 50% (IC50) values were determined from selected responding kinases, e.g., VEGFR1 and RET. TIE2 kinase inhibition was measured with a homogeneous time-resolved fluorescence (HTRF) assay using a recombinant fusion protein of glutathione-S-transferase, the intracellular domain of TIE2 and the peptide biotin-Ahx-EPKDDAYPLYSDFG as substrate.
• Preparation and Storage: Store at -20 degree C for 3 years powder; -80 degree C for 2 years in solvent

Related Product Information for Regorafenib monohydrate, inhibitor

Regorafenib Monohydrate is a novel oral multikinase inhibitor with IC50 values of 13, 4.2, 46, 22, 7, 1.5, 2.5, 28, 19nM for VEGFR1, murine VEGFR2, murine VEGFR3, PDGFR-beta, KIT, RET, RAF-1, B-RAF and B-RAF(V600E) respectively.

Product Categories/Family for Regorafenib monohydrate, inhibitor

Angiogenesis; Tyrosine Kinase/Adaptors; Apoptosis; MAPK

References

Wilhelm SM, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer, 2011, 129(1), 245-255.
Carr BI, et al. Fluoro-Sorafenib (Regorafenib) effects on hepatoma cells: growth inhibition, quiescence, and recovery. J Cell Physiol, 2013, 228(2), 292-297.
Zopf D, et al. Pharmacologic activity and pharmacokinetics of metabolites of regorafenib in preclinical models. Cancer Med. 2016 Nov;5(11):3176-3185.