BLU9931

SKU: orb1226130

Description

BLU9931 (BLU-9931) is a potent, selective, irreversible inhibitor of FGFR4 with IC50 of 3 nM, shows much weaker activity for FGFR1 (IC50=591 nM), FGFR2 (IC50=493 nM) and FGFR3 (IC50=150 nM); potently and selectively inhibits FGFR4 signaling and cell proliferation in HCC cell lines with an activated FGFR4 signaling pathway (Huh-7 cell IC50=110 nM, JHH-7 IC50=20 nM); shows remarkable antitumor activity in mice bearing HCC tumor xenograft that overexpresses FGF19.Lung Cancer Phase 1 Clinical.

Key Properties

• CAS Number: 1538604-68-0
• MW: 509.3839
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₂Cl₂N₄O₃
• SMILES: COC1=CC(OC)=C(Cl)C(=C1Cl)C1=CC2=CN=C(NC3=C(C)C=CC=C3NC(=O)C=C)N=C2C=C1
• Target: FGFR
• Solubility: DMSO: 17 mg/mL

Bioactivity

• In Vivo:
  BLU9931 (10-100 mg/kg; oral administration; twice every day; for 21 days; mice) treatment demonstrates antitumor activity in HCC xenograft models. Animal model: Mice injected with Hep 3B cells. Dosage: 10 mg/kg, 30 mg/kg or 100 mg/kg. Administration: Oral administration; twice every day; for 21 days. Result: Resulted in dose-dependent growth inhibition of Hep 3B tumors. Prevented weight loss in a dose-dependent manner.
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• In Vitro:
  BLU9931 inhibits proliferation of HCC cell lines that express an intact FGFR4 signaling complex, with EC50s of 0.07 μM, 0.11 μM and 0.02 μM for Hep 3B, HuH7 and JHH7 cells, respectively. BLU9931 (0.3-300 nM; 1 hour; MDA-MB-453 and Hep 3B cells) treatment demonstrates potent, dose-dependent reduction of phosphorylation of FGFR4 signaling pathway components, including fibroblast growth factor receptor substrate 2 (FRS2), MAPK, and AKT in MDA-MB-453 cells. BLU9931 shows dose-dependent inhibition of the signaling cascade downstream of FGFR4. BLU9931 exhibits potent inhibition of phosphorylation of the FGFR4 pathway components in Hep 3B cells. BLU9931 treatment leads to induction of caspase-3/7 activity, indicative of induction of apoptosis that results in inhibition of signaling downstream of FGFR4.BLU9931 (100 nM; 0 -24 hours; Hep 3B cells) treatment increases CYP7A1 mRNA expression and the expression of the proliferative marker EGR1 is inhibited. Western blot analysis. Cell line: MDA-MB-453 and Hep 3B cells. Concentration: 0.3 nM, 1 nM, 3 nM, 10 nM, 30 nM, 100 nM, 300 nM Incubation time: 1 hour. Result: Demonstrated potent, dose-dependent reduction of phosphorylation of FGFR4 signaling pathway components, including fibroblast growth factor receptor substrate 2 (FRS2), MAPK, and AKT in MDA-MB-453 and Hep 3B cells. RT-PCR Cell line: Hep 3B cells. Concentration: 100 nM. Incubation time: 0 hour, 4 hours, 8 hour, 24 hours. Result: Increased CYP7A1 mRNA expression. And the expression of the proliferative marker EGR1 was inhibited.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BLU-9931

Quick Database Links

Gene Symbol

FGFR