BLU-9931


Catalog No. size PriceQuantity
M6481-2 2mg solid $81
M6481-10 10mg solid $320

Description

Cas:1538604-68-0

Product Information:

BLU-9931 is a potent and irreversible small-molecule inhibitor of FGFR4, as a targeted therapy to treat patients with HCC whose tumors have an activated FGFR4 signaling pathway. 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. Approximately one third of patients with HCC whose tumors express FGF19 together with FGFR4 and its coreceptor klotho β (KLB) could potentially respond to treatment with an FGFR4 inhibitor.

 

Chemical Formula: C26H22Cl2N4O3

 

Exact Mass: 508.1069

 

Molecular Weight: 509.38

 

Elemental Analysis: C, 61.31; H, 4.35; Cl, 13.92; N, 11.00; O, 9.42

 

Synonym:

 

BLU9931

BLU-9931

BLU 9931

 

Chemical Name:

N-(2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)-3-methylphenyl)acrylamide

 

InChi Key:

TXEBNKKOLVBTFK-UHFFFAOYSA-N

 

InChi Code:

InChI=1S/C26H22Cl2N4O3/c1-5-21(33)30-18-8-6-7-14(2)25(18)32-26-29-13-16-11-15(9-10-17(16)31-26)22-23(27)19(34-3)12-20(35-4)24(22)28/h5-13H,1H2,2-4H3,(H,30,33)(H,29,31,32)

 

Smiles Code:

C=CC(NC1=CC=CC(C)=C1NC2=NC=C3C=C(C4=C(Cl)C(OC)=CC(OC)=C4Cl)C=CC3=N2)=O

 

 

Technical Data:

 

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: 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.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

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.

In Vivo:

BLU9931 (10-100 mg/kg; oral administration; twice every day; for 21 days; mice) treatment demonstrates antitumor activity in HCC xenograft models.

 

 

References

 

  1. Packer LM, Pollock PM. Paralog-Specific Kinase Inhibition of FGFR4: Adding to the Arsenal of Anti-FGFR Agents. Cancer Discov. 2015 Apr;5(4):355-7. doi: 10.1158/2159-8290.CD-15-0246. PubMed PMID: 25847957.

 

  1. Hagel M, Miduturu C, Sheets M, Rubin N, Weng W, Stransky N, Bifulco N, Kim JL, Hodous B, Brooijmans N, Shutes A, Winter C, Lengauer C, Kohl NE, Guzi T. First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway. Cancer Discov. 2015 Apr;5(4):424-37. doi: 10.1158/2159-8290.CD-14-1029. Epub 2015 Mar 16. PubMed PMID: 25776529.

 

Products are for research use only. Not for human use.

 

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