FUTIBATINIB

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Synonyms
Status
Molecule Category UNKNOWN
UNII 4B93MGE4AL

Structure

InChI Key KEIPNCCJPRMIAX-HNNXBMFYSA-N
Smiles C=CC(=O)N1CC[C@H](n2nc(C#Cc3cc(OC)cc(OC)c3)c3c(N)ncnc32)C1
InChI
InChI=1S/C22H22N6O3/c1-4-19(29)27-8-7-15(12-27)28-22-20(21(23)24-13-25-22)18(26-28)6-5-14-9-16(30-2)11-17(10-14)31-3/h4,9-11,13,15H,1,7-8,12H2,2-3H3,(H2,23,24,25)/t15-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C22H22N6O3
Molecular Weight 418.46
AlogP 1.78
Hydrogen Bond Acceptor 8.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 4.0
Polar Surface Area 108.39
Molecular species NEUTRAL
Aromatic Rings 3.0
Heavy Atoms 31.0

Bioactivity

Mechanism of Action Action Reference
Fibroblast growth factor receptor inhibitor INHIBITOR PubMed Other
Protein: Fibroblast growth factor receptor
Description: Fibroblast growth factor receptor 1
Organism : Homo sapiens
P11362 ENSG00000077782
Protein: Fibroblast growth factor receptor
Description: Fibroblast growth factor receptor 2
Organism : Homo sapiens
P21802 ENSG00000066468
Protein: Fibroblast growth factor receptor
Description: Fibroblast growth factor receptor 4
Organism : Homo sapiens
P22455 ENSG00000160867
Protein: Fibroblast growth factor receptor
Description: Fibroblast growth factor receptor 3
Organism : Homo sapiens
P22607 ENSG00000068078
Assay Description Organism Bioactivity Reference
Inhibition Assay: Purified recombinant human FGFR4 protein was purchased from Carna Biosciences, Inc. When setting conditions for the measurement of the inhibitory effect of the compounds on FGFR4 kinase activity, a biotinylated peptide (biotin-EEPLYWSFPAKKK) was synthesized for use as a substrate by utilizing the amino acid sequence of FL-Peptide 22 (Caliper Life Sciences, Inc.) with biotin. The purified recombinant human FGFR4 protein used in the test was purchased from Carna Biosciences, Inc. In the measurement of the inhibitory effect of the compounds, first, a test compound was gradually diluted with dimethylsulfoxide (DMSO) to a concentration 20 times higher than the final concentration. Next, the purified human FGFR4 protein, substrate peptide (final concentration: 250 nM), magnesium chloride (final concentration: 5 mM), ATP (final concentration: 190 .mu.M), and the test compound DMSO solution (final concentration of DMSO: 5%) were added to a reaction buffer. Homo sapiens 3.6 nM
Inhibition Assay: When setting conditions for the measurement of the inhibitory effect of the compounds on FGFR2 kinase activity, FL-Peptide 22 (Caliper Life Sciences, Inc.) was used as a substrate. The purified recombinant human FGFR2 protein used in the test was purchased from Carna Biosciences, Inc. In the measurement of the inhibitory effect of the compounds, first, a test compound was gradually diluted with dimethylsulfoxide (DMSO) to a concentration that was 20 times higher than the final concentration. Next, the purified human FGFR2 protein, FL-Peptide 22 (final concentration: 1.5 .mu.M), magnesium chloride (final concentration: 5 mM), ATP (final concentration: 75 .mu.M), and the test compound DMSO solution (final concentration of DMSO: 5%) were added to a reaction buffer (15 mM Tris-HCl pH 7.5, 0.01% Tween-20, 2 mM DTT), and the mixture was incubated at 25.degree. C. for 120 minutes to perform a kinase reaction. EDTA (final concentration: 30 mM) diluted with a separation buffer. Homo sapiens 1.1 nM
Inhibition Assay: Purified recombinant human FGFR3 protein was purchased from Carna Biosciences, Inc. When setting conditions for the measurement of the inhibitory effect of the compounds on FGFR3 kinase activity, a biotinylated peptide (biotin-EEPLYWSFPAKKK) was synthesized for use as a substrate by utilizing the amino acid sequence of FL-Peptide 22 (Caliper Life Sciences, Inc.) with biotin. The purified recombinant human FGFR3 protein used in the test was purchased from Carna Biosciences, Inc. In the measurement of the inhibitory effect of the compounds, first, a test compound was gradually diluted with dimethylsulfoxide (DMSO) to a concentration 20 times higher than the final concentration. Next, the purified human FGFR3 protein, substrate peptide (final concentration: 250 nM), magnesium chloride (final concentration: 5 mM), ATP (final concentration: 190 .mu.M), and the test compound DMSO solution (final concentration of DMSO: 5%) were added to a reaction buffer. Homo sapiens 0.5 nM
Inhibition Assay: Purified recombinant human FGFR4 protein was purchased from Carna Biosciences, Inc. When setting conditions for the measurement of the inhibitory effect of the compounds on FGFR4 kinase activity, a biotinylated peptide (biotin-EEPLYWSFPAKKK) was synthesized for use as a substrate by utilizing the amino acid sequence of FL-Peptide 22 (Caliper Life Sciences, Inc.) with biotin. The purified recombinant human FGFR4 protein used in the test was purchased from Carna Biosciences, Inc. In the measurement of the inhibitory effect of the compounds, first, a test compound was gradually diluted with dimethylsulfoxide (DMSO) to a concentration 20 times higher than the final concentration. Next, the purified human FGFR4 protein, substrate peptide (final concentration: 250 nM), magnesium chloride (final concentration: 5 mM), ATP (final concentration: 190 .mu.M), and the test compound DMSO solution (final concentration of DMSO: 5%) were added to a reaction buffer. None 3.4 nM
Inhibition of human FGFR1 (459 to 765 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay Homo sapiens 2.2 nM
Inhibition of human FGFR2 (458 to 768 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay Homo sapiens 4.2 nM
Inhibition of human FGFR3 (450 to 758 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay Homo sapiens 0.53 nM
Inhibition of human FGFR4 (445 to 753 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay Homo sapiens 5.2 nM
Antiproliferative activity against human NCI-H1581 cells expressing FGFR1 assessed as inhibition of cell growth measured after 96 hrs by CCK-8 assay Homo sapiens 7.0 nM
Antiproliferative activity against human SNU-16 cells expressing FGFR2 assessed as inhibition of cell growth measured after 96 hrs by CCK-8 assay Homo sapiens 4.0 nM
Antiproliferative activity against human SK-HEP1 cells expressing FGFR4 assessed as inhibition of cell growth measured after 96 hrs by CCK-8 assay Homo sapiens 152.0 nM

Cross References

Resources Reference
ChEMBL CHEMBL3701238
DrugBank DB15149
FDA SRS 4B93MGE4AL
Guide to Pharmacology 9786
PDB TZ0
PubChem 71621331
SureChEMBL SCHEMBL15345470
ZINC ZINC000207800318
CONTENTS