GILTERITINIB

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Synonyms
Status
Molecule Category UNKNOWN
ATC L01EX13
UNII 66D92MGC8M

Structure

InChI Key GYQYAJJFPNQOOW-UHFFFAOYSA-N
Smiles CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(OC)c2)nc1NC1CCOCC1
InChI
InChI=1S/C29H44N8O3/c1-4-23-28(31-20-9-17-40-18-10-20)34-29(26(33-23)27(30)38)32-21-5-6-24(25(19-21)39-3)37-11-7-22(8-12-37)36-15-13-35(2)14-16-36/h5-6,19-20,22H,4,7-18H2,1-3H3,(H2,30,38)(H2,31,32,34)

Physicochemical Descriptors

Property Name Value
Molecular Formula C29H44N8O3
Molecular Weight 552.72
AlogP 2.7
Hydrogen Bond Acceptor 10.0
Hydrogen Bond Donor 3.0
Number of Rotational Bond 9.0
Polar Surface Area 121.11
Molecular species NEUTRAL
Aromatic Rings 2.0
Heavy Atoms 40.0

Bioactivity

Mechanism of Action Action Reference
Tyrosine-protein kinase receptor FLT3 inhibitor INHIBITOR Other PubMed FDA PubMed
Protein: Tyrosine-protein kinase receptor UFO
Description: Tyrosine-protein kinase receptor UFO
Organism : Homo sapiens
P30530 ENSG00000167601
Protein: Tyrosine-protein kinase receptor FLT3
Description: Receptor-type tyrosine-protein kinase FLT3
Organism : Homo sapiens
P36888 ENSG00000122025
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Axl family
- 1-11 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase PDGFR family
- 0-0 - - -
Transcription factor
- 9 - - -
Assay Description Organism Bioactivity Reference
Inhibition Assay: A partial protein of only a kinase domain of RET protein was purchased from Carna Biosciences Inc., Japan. The phosphorylation activity toward a peptide substrate was investigated using an EZ reader (Caliper). Test compounds were each mixed with a protein solution to give 8 final concentrations from 100 nM to 0.03 nM, followed by addition of a mixed liquid of ATP and substrate peptide (Caliper) and reaction for 30 minutes. The ATP concentration used was 100 µM. A reaction liquid which contained protein but no test compound (in which the solvent DMSO alone was added at 0.8% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition. In the absence of the test compound, the phosphorylation peptide peak without ATP addition and with ATP addition was assumed to be 100% inhibition and 0% inhibition, respectively. Homo sapiens 3.4 nM
Inhibition Assay: A partial protein of only a kinase domain of ROS protein was purchased from Carna Biosciences Inc., Japan, and tests were conducted as in Test Example 5, except that the ATP concentration in the mixed solution of ATP and substrate peptide (Caliper) was 50 uM. Test Example 5: A partial protein of only a kinase domain of RET protein was purchased from Carna Biosciences Inc., Japan. The phosphorylation activity toward a peptide substrate was investigated using an EZ reader (Caliper). Test compounds were each mixed with a protein solution to give 8 final concentrations from 100 nM to 0.03 nM, followed by addition of a mixed liquid of ATP and substrate peptide (Caliper) and reaction for 30 minutes. The ATP concentration used was 100 µM. A reaction liquid which contained protein but no test compound (in which the solvent DMSO alone was added at 0.8% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition. None 1.9 nM
Inhibition Assay: A recombinant retrovirus was created from expression plasmid FLAG-EML4-ALKv1/pMX-iresCD8 in which cDNA for EMLA-ALK fusion protein v1 was integrated, and injected into mouse lymphoid cell line BA/F3 cells. Using a magnetic bead reagent for cell separation and a purification column (anti-CD8 monoclonal antibody immobilized on magnetic beads and a MiniMACS purification column; both are products of MilteDyi Biotec Inc.), cell surface CD8-expressing cells were purified to establish EML4-ALK fusion protein v1-expressing BA/F3 cells. From the cells, EML4-ALK fusion protein v1 was purified and subjected to kinase activity evaluation. EML4-ALK fusion protein v1 was investigated for its phosphorylation activity toward a peptide substrate by using a kinase activity detection kit (HTRF KinEASE-TK; Cisbio Inc.). Test compounds were each added to a reaction solution containing the enzyme protein to give 8 final concentrations from 1000 nM to 0.3 nM, followed by addition of ATP. None 1.5 nM
Inhibition Assay: A partial protein of only a kinase domain of FLT3 protein was purchased from Carna Biosciences Inc., Japan, and tests were conducted as in Test Example 5. Test Example 5: A partial protein of only a kinase domain of RET protein was purchased from Carna Biosciences Inc., Japan. The phosphorylation activity toward a peptide substrate was investigated using an EZ reader (Caliper). Test compounds were each mixed with a protein solution to give 8 final concentrations from 100 nM to 0.03 nM, followed by addition of a mixed liquid of ATP and substrate peptide (Caliper) and reaction for 30 minutes. The ATP concentration used was 100 µM. A reaction liquid which contained protein but no test compound (in which the solvent DMSO alone was added at 0.8% in place of the test compound) was prepared, followed by reaction in the same manner with or without ATP addition. Homo sapiens 0.41 nM
Inhibition of AXL (unknown origin) Homo sapiens 1.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 25.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 208.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 39.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 152.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 184.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 46.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 121.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 572.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 191.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 207.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 169.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 421.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 811.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 960.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 202.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 432.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 241.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 188.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 7.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 9.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 7.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 221.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 502.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 600.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 536.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 108.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 244.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 605.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 202.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 512.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 263.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 736.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 430.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 804.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 188.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 247.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 510.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 48.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 18.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 591.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 510.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 11.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 759.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 50.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 482.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 451.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 495.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 68.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 149.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 295.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 230.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 39.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 464.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 6.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 445.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 0.23 %
Inhibition of N-terminal GST-tagged human FLT3 (564 to 993 residues) cytoplasmic domain expressed in baculovirus expression system by ELISA Homo sapiens 0.29 nM
Inhibition of N-terminal GST-tagged human AXL (464 to 885 residues) cytoplasmic domain expressed in baculovirus expression system by ELISA Homo sapiens 0.73 nM
Inhibition of recombinant FLAG-tagged EML4-ALK fusion protein (unknown origin) expressed in mouse BA/F3 cells using peptide substrate and ATP incubated for 1 hr by HTRF assay Homo sapiens 1.5 nM
Inhibition of recombinant FLAG-tagged EML4-ALK fusion protein (unknown origin) expressed in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 2 days by alamar blue dye based assay Homo sapiens 5.7 nM
Inhibition of AXL (unknown origin) using poly (Glu, Tyr) as substrate after 60 mins by ELISA Homo sapiens 11.3 nM
Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay Homo sapiens 8.5 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 14.54 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.03 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.03 %
Antiproliferative activity against human A549 cells assessed as cell growth inhibition at 1 uM by WST assay relative to control Homo sapiens 4.05 %
Antiproliferative activity against human MDA-MB-231 cells assessed as cell growth inhibition at 1 uM by WST assay relative to control Homo sapiens 42.13 %
Antiproliferative activity against human HCT-116 cells assessed as cell growth inhibition at 1 uM by WST assay relative to control Homo sapiens 45.1 %
Antiproliferative activity against human PC3 cells assessed as cell growth inhibition at 1 uM by WST assay relative to control Homo sapiens 41.76 %
Antiproliferative activity against human SK-OV-3 cells assessed as cell growth inhibition at 1 uM by WST assay relative to control Homo sapiens 23.33 %
Inhibition of FLT3 expressed in human SEMK2 cells assessed as reduction in FLT3 phosphorylation incubated for 1 hr by immunoblotting analysis Homo sapiens 0.29 nM
Inhibition of wild type FLT3 (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay Homo sapiens 10.0 nM
Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay Homo sapiens 2.0 nM
Inhibition of AXL (unknown origin) using poly [Glu, Tyr] 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA Homo sapiens 4.6 nM
Antiproliferative activity against mouse BaF3/TEL-AXL cells incubated for 72 hrs by SRB or CCK8 assay Mus musculus 7.6 nM

Cross References

Resources Reference
ChEBI 145372
ChEMBL CHEMBL3301622
DrugBank DB12141
DrugCentral 5306
FDA SRS 66D92MGC8M
Guide to Pharmacology 8708
PDB C6F
PubChem 49803313
SureChEMBL SCHEMBL282229
ZINC ZINC000113476229
CONTENTS