| Questions And Answer | Back Directory | [Synthesis]
A mixture of K2CO3 (6 g, 43.5 mmol), 8-bromo-3-chloroisoquinoline-5-yltrifluoromethanesulfonate (17 g), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborane (7.30 g), and Pd(dppf)Cl2·CH2Cl2 (2.83 g, 3.48 mmol) in dioxane (200/20 mL) was stirred at 45°C for 3 hours. The mixture was diluted with 500 mL of ethyl acetate. The mixture was washed twice with brine (200 mL). The organic layer was dried over Na₂SO₄. The organic layer was concentrated under vacuum. The residue was purified by silica gel column chromatography with petroleum ether:ethyl acetate = 20:1 to give the title compound BLU-945. |
| Chemical Properties | Back Directory | [Boiling point ]
784.6±70.0 °C(Predicted) | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: Sparingly soluble: 1-10 mg/ml
Ethanol: Slightly soluble: 0.1-1 mg/ml | [form ]
Solid | [pka]
7.87±0.10(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
LIMFPAAAIVQRRD-MCEZSBKONA-N | [SMILES]
C(C1=CC=C(N2C[C@H](CS(=O)(=O)C)[C@H]2C)C2C=NC(NC3C=CN=C(N4CC[C@@H](OC)[C@@H](F)C4)N=3)=CC1=2)(C)C |&1:7,13,28,31,r| |
| Hazard Information | Back Directory | [Description]
BLU-945 is a potent, highly selective, reversible, and orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It can effectively inhibit EGFR with L858R and/or exon 19 deletion mutation, T790M mutation, and C797S mutation. BLU-945 can be used for research on lung cancer, including non-small cell lung cancer (NSCLC)[1]. | [Chemical Properties]
IUPAC/Chemical Name: N-(2-((3S,4R)-3-fluoro-4-methoxypiperidin-1-yl)pyrimidin-4-yl)-5-isopropyl-8-((2R,3S)-2-methyl-3-((methylsulfonyl)methyl)azetidin-1-yl)isoquinolin-3-amine. | [Side effects]
According to clinical studies of BLU-945, common side effects of BLU-945 monotherapy include: rash, diarrhoea, nausea, vomiting, headache, dry skin, onychomycosis, and elevated alanine aminotransferase and aspartate aminotransferase.
Common side effects of the combination of BLU-945 and ositinib include: headache, nausea, fatigue, decreased appetite, vomiting, diarrhoea, dry skin, acne-like dermatitis and onychomycosis. | [in vitro]
BLU-945 has inhibitory activity against the EGFRm/T790M double and EGFRm/T790M/C797Striple mutants with IC50 value range from 1.2-4.4 nM.
BLU-945 (0- 10 mM, 4 h) inhibit EGFR phosphorylation in the EGFR L858R/T790M/C797S, and EGFR ex19del/T790M/C797S mutant cell lines. | [References]
[1] Y. Elamin. “BLU-945 monotherapy and in combination with osimertinib (OSI) in previously treated patients with advanced EGFR-mutant (EGFRm) NSCLC in the phase 1/2 SYMPHONY study.” Journal of Clinical Oncology (2023).
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