product name BLU9931
Description: BLU9931 is a potent, selective, and irreversible small-molecule inhibitor of FGFR4 with IC50 of 3 nM, it displayed about 297-, 184-, and 50-fold selectivity over FGFR1/2/3, respectively. BLU9931 is exquisitely selective for FGFR4 versus other FGFR family members and all other kinases. BLU9931 shows remarkable antitumor activity in mice bearing an HCC tumor xenograft that overexpresses FGF19 due to amplification as well as a liver tumor xenograft that overexpresses FGF19 mRNA but lacks FGF19 amplification.
References: Cancer Discov. 2015 Apr;5(4):424-37.
509.38
Formula
C26H22Cl2N4O3
CAS No.
1538604-68-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 4 mg/mL (7.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% carboxymethylcellulose+1% Tween 80 as a suspension: 30mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420626
| In Vitro |
In vitro activity: In MDA-MB-453 cells, BLU9931 potently inhibits phosphorylation of FGFR4 signaling pathway. BLU9931 inhibits proliferation of HCC cell lines that express an intact FGFR4 signaling complex, such as Hep 3B, HUH-7, and JHH-7 cell lines, with EC50 of <1 μM. BLU9931 also inhibits proliferation in PDX-derived cell lines with an intact FGFR4 signaling pathway. Kinase Assay: FGFR kinase inhibition assays are performed at KM for ATP. Picomolar to low nanomolar concentrations of FGFR proteins are incubated in 1× Kinase Reaction Buffer (KRB) with 1 μM of CSKtide and 50 to 250 of μM ATP at 25°C for 90 minutes in the presence or absence of a dosed concentration series of inhibitor. All reactions are terminated by the addition of Stop buffer, and plates are read on a Caliper EZReader2. IC50 values are fit with a four-parameter log[Inhibitor] versus response model with floating Hill Slope. Cell Assay: Established (Hep 3B, HUH-7, JHH-7, PLC/PRF/5, SK-HEP-1, SNU-182, SNU-387, SNU-398, SNU-423, SNU-449, SNU-878 cells) and PDX-derived HCC cell lines are seeded in 96-well plates in respective growth media, allowed to attach overnight, and treated with a dilution series of test compounds for two cell-doubling times. Cell viability is determined by CellTiter-Glo, and results represented as background-subtracted relative light units normalized to a DMSO-treated control. Relative EC50 values are determined at 50% inhibition between the top and bottom plateau of the dose–response curve. |
|---|---|
| In Vivo | In mice bearing the FGF19-amplified Hep 3B liver tumors, BLU9931 (300 mg/kg, p.o.) leads to tumor regression and prevents this weight loss induced by tumors. In mice bearing the FGF19-overexpressing PDX-derived LIXC012 xenografts, treatment with BLU9931 (300 mg/kg, p.o.) also leads to tumor regression. |
| Animal model | Mice injected with LIXC012 tumors |
| Formulation & Dosage | Formulated in 0.5% carboxymethylcellulose/1% Tween 80 as a suspension; 300 mg/kg; oral gavage |
| References | Cancer Discov. 2015 Apr;5(4):424-37. |
