BLU-554

BLU-554, also known as Fisogatinib, is a fibroblast growth factor receptor 4 (FGFR4) inhibitor potentially for the treatment of hepatocellular carcinoma and cholangiocarcinoma. BLU-554 demonstrates clinical benefit and tumor regression in patients with HCC with aberrant FGF19 expression.

Product information

CAS Number: 1707289-21-1

Molecular Weight: 503.38

Formula: C24H24Cl2N4O4

Synonym:

Fisogatinib

BLU 554

BLU554

BLU-554

Chemical Name: N-((3S,4S)-3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)tetrahydro-2H-pyran-4-yl)acrylamide

Smiles: COC1=CC(OC)=C(Cl)C(C2=CC3=CN=C(N[C@@H]4COCC[C@@H]4NC(=O)C=C)N=C3C=C2)=C1Cl

InChiKey: MGZKYOAQVGSSGC-DLBZAZTESA-N

InChi: InChI=1S/C24H24Cl2N4O4/c1-4-20(31)28-16-7-8-34-12-17(16)30-24-27-11-14-9-13(5-6-15(14)29-24)21-22(25)18(32-2)10-19(33-3)23(21)26/h4-6,9-11,16-17H,1,7-8,12H2,2-3H3,(H,28,31)(H,27,29,30)/t16-,17+/m0/s1

Technical Data

Appearance: Solid Power

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

Solubility: DMSO: 100 mg/mLwarmed(198.65 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Tissue distribution of BLU-554 (10 mg/kg; oral gavage; for 4 hours; FVB/NRj mice) in wild-type mice is as follows; tissue concentrations decreases in the order liver > kidney > small intestine > spleen > brain. The high BLU-554 liver-to-plasma ratio suggests there is a relatively high amount of the drug being transported into the liver.

References:

1. Subbiah V, Pal SK. Precision Oncology for Hepatocellular Cancer: Slivering the Liver by FGF19-FGF4-KLB Pathway Inhibition. Cancer Discov. 2019 Dec;9(12):1646-1649. doi: 10.1158/2159-8290.CD-19-1156. Erratum in: Cancer Discov. 2020 Feb;10(2):326. PMID: 31792121.
2. Roskoski R Jr. The role of fibroblast growth factor receptor (FGFR) protein- tyrosine kinase inhibitors in the treatment of cancers including those of the urinary bladder. Pharmacol Res. 2020 Jan;151:104567. doi: 10.1016/j.phrs.2019.104567. Epub 2019 Nov 23. PMID: 31770593.
3. Li W, Sparidans R, El-Lari M, Wang Y, Lebre MC, Beijnen JH, Schinkel AH. P-glycoprotein (ABCB1/MDR1) limits brain accumulation and Cytochrome P450-3A (CYP3A) restricts oral availability of the novel FGFR4 inhibitor fisogatinib (BLU-554). Int J Pharm. 2020 Jan 5;573:118842. doi: 10.1016/j.ijpharm.2019.118842. Epub 2019 Nov 20. PMID: 31759109.

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