BLU9931

Catalog No.S7819 Batch:S781901

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Technical Data

Formula

C26H22Cl2N4O3
Molecular Weight 509.38 CAS No. 1538604-68-0
Solubility (25°C)* In vitro DMSO 4 mg/mL (7.85 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description BLU9931 is a potent, selective, and irreversible FGFR4 inhibitor with IC50 of 3 nM, about 297-, 184-, and 50-fold selectivity over FGFR1/2/3, respectively.
Targets
FGFR4 [1]
(Cell-free assay)		 FGFR3 [1]
(Cell-free assay)
3 nM 150 nM
In vitro 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. [1]
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. [1]

Protocol (from reference)

Kinase Assay:[1]
  • FGFR1-4 Biochemical Assays

    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:[1]
  • Cell lines

    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

  • Concentrations

    ~10 μM

  • Incubation Time

    72-120 hours

  • Method

    Established 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.
Animal Study:[1]
  • Animal Models

    Mice bearing LIXC012 tumors

  • Dosages

    ~300 mg/kg

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Cancer Science, 2018, doi:10.1111/cas.13569]

Selleck's BLU9931 has been cited by 18 publications

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling [ J Exp Clin Cancer Res, 2023, 42(1):96] PubMed: 37085881
Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells [ Cell Death Dis, 2023, 10.1038/s41419-023-06240-x] PubMed: 37938546
Fibroblast Growth Factor 23 Signaling Does Not Increase Inflammation from Pseudomonas aeruginosa Infection in the Cystic Fibrosis Bronchial Epithelium [ Medicina (Kaunas), 2023, 10.3390/medicina59091635] PubMed: 37763754
Fibroblast Growth Factor (FGF) 23 and FGF Receptor 4 promote cardiac metabolic remodeling in chronic kidney disease [ Res Sq, 2023, rs.3.rs-3705543] PubMed: 38196615
Fibroblast Growth Factor 23 Signaling Does Not Increase Inflammation from Pseudomonas aeruginosa Infection in the Cystic Fibrosis Bronchial Epithelium [ Medicina (Kaunas), 2023, 59(9)1635] PubMed: 37763754
18F-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis [ Theranostics, 2022, 12(14):6395-6408] PubMed: 36168616
Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma [ Br J Cancer, 2022, 10.1038/s41416-022-01973-6] PubMed: 36097178
BLU-554, A selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro [ Biochem Biophys Res Commun, 2022, 595:22-27] PubMed: 35093636
Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models [ Breast Cancer Res, 2021, 23(1):82] PubMed: 34344433
Excessive fibroblast growth factor 23 promotes renal fibrosis in mice with type 2 cardiorenal syndrome [ Aging (Albany NY), 2021, 13(2):2982-3009] PubMed: 33460402

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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