BRIVANIB

/static/temp/default.svg Search structure
Synonyms
Status
Molecule Category UNKNOWN
UNII DDU33B674I
EPA CompTox DTXSID60215294

Structure

InChI Key WCWUXEGQKLTGDX-LLVKDONJSA-N
Smiles Cc1cc2c(F)c(Oc3ncnn4cc(OC[C@@H](C)O)c(C)c34)ccc2[nH]1
InChI
InChI=1S/C19H19FN4O3/c1-10-6-13-14(23-10)4-5-15(17(13)20)27-19-18-12(3)16(26-8-11(2)25)7-24(18)22-9-21-19/h4-7,9,11,23,25H,8H2,1-3H3/t11-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C19H19FN4O3
Molecular Weight 370.38
AlogP 3.52
Hydrogen Bond Acceptor 6.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 5.0
Polar Surface Area 84.67
Molecular species NEUTRAL
Aromatic Rings 4.0
Heavy Atoms 27.0

Bioactivity

Mechanism of Action Action Reference
Fibroblast growth factor receptor inhibitor INHIBITOR PubMed PubMed
Protein: Fibroblast growth factor receptor
Description: Fibroblast growth factor receptor 1
Organism : Homo sapiens
P11362 ENSG00000077782
Protein: Vascular endothelial growth factor receptor
Description: Vascular endothelial growth factor receptor 1
Organism : Homo sapiens
P17948 ENSG00000102755
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
Protein: Vascular endothelial growth factor receptor
Description: Vascular endothelial growth factor receptor 3
Organism : Homo sapiens
P35916 ENSG00000037280
Protein: Vascular endothelial growth factor receptor
Description: Vascular endothelial growth factor receptor 2
Organism : Homo sapiens
P35968 ENSG00000128052
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Cytochrome P450 Cytochrome P450 family 1 Cytochrome P450 family 1A Cytochrome P450 1A2
- - - - 55-60
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A4
- 18000-40000 - - 50-50
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A5
- - - - 50-50
Enzyme Kinase Protein Kinase AGC protein kinase group AGC protein kinase YANK family
- - 3900 - -
Enzyme Kinase Protein Kinase CAMK protein kinase group CAMK protein kinase unique family
- - 3200 - -
Enzyme Kinase Protein Kinase Other protein kinase group Other protein kinase NKF4 family
- - 26 - -
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE11 family
- - 500 - -
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE20 family STE protein kinase KHS subfamily
- - 1400 - -
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE20 family STE protein kinase MSN subfamily
- - 160 - -
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE20 family STE protein kinase SLK subfamily
- - 170 - -
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE7 family
- - 3100 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Abl family
- - 390-4100 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase DDR family
- - 160 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase EGFR family
- - 2600-5300 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Eph family
- - 1700 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase FGFR family
- 28-148 150-160 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase PDGFR family
- - 12-4000 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Ret family
- - 360-390 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Src family
- - 1100 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Tie family
- - 1100 - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase VEGFR family
- 25-26 10 26 -
Enzyme Kinase Protein Kinase TKL protein kinase group TKL protein kinase RIPK family
- - 2900 - -
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel
- 18000 - - -
Membrane receptor
- - 1400 - -
Assay Description Organism Bioactivity Reference
Inhibitory activity against VEGFR2 Homo sapiens 25.0 nM Inhibitory activity against VEGFR2 Homo sapiens 26.0 nM
Inhibitory activity against Flk1 Mus musculus 89.0 nM Inhibitory activity against Flk1 Mus musculus 28.0 nM
Inhibitory activity against VEGFR1 Homo sapiens 380.0 nM Inhibitory activity against VEGFR1 Homo sapiens 60.0 nM
Inhibitory activity against FGFR1 Homo sapiens 148.0 nM
Inhibition of human VEGFR2 Homo sapiens 25.0 nM
Binding constant for STK35 kinase domain None 26.0 nM
Binding constant for EPHA6 kinase domain None 190.0 nM
Binding constant for MAP4K4 kinase domain None 590.0 nM
Binding constant for FGFR3 kinase domain None 160.0 nM
Binding constant for FGFR3(G697C) kinase domain None 150.0 nM
Binding constant for KIT kinase domain None 36.0 nM
Binding constant for KIT(L576P) kinase domain None 54.0 nM
Binding constant for KIT(V559D) kinase domain None 35.0 nM
Binding constant for KIT(V559D,T670I) kinase domain None 17.0 nM
Binding constant for KIT(V559D,V654A) kinase domain None 12.0 nM
Binding constant for TIE2 kinase domain None 440.0 nM
Binding constant for MINK kinase domain None 310.0 nM
Binding constant for DDR1 kinase domain None 160.0 nM
Binding constant for FLT1 kinase domain None 10.0 nM
Binding constant for FLT4 kinase domain None 56.0 nM
Binding constant for VEGFR2 kinase domain None 5.0 nM
Binding constant for PDGFRB kinase domain None 50.0 nM
Binding constant for ABL1(E255K)-phosphorylated kinase domain None 580.0 nM
Binding constant for ABL1(H396P)-non phosphorylated kinase domain None 390.0 nM
Binding constant for ABL1(H396P)-phosphorylated kinase domain None 640.0 nM
Binding constant for ABL1(M351T)-phosphorylated kinase domain None 450.0 nM
Binding constant for ABL1(T315I)-phosphorylated kinase domain None 450.0 nM
Binding constant for ABL1-phosphorylated kinase domain None 640.0 nM
Binding constant for LOK kinase domain None 220.0 nM
Binding constant for PDGFRA kinase domain None 11.0 nM
Binding constant for SLK kinase domain None 170.0 nM
Binding constant for TNIK kinase domain None 160.0 nM
Binding constant for RET kinase domain None 390.0 nM
Binding constant for RET(M918T) kinase domain None 360.0 nM
Binding constant for FGFR4 kinase domain None 600.0 nM
Binding constant for FGFR2 kinase domain None 110.0 nM
Binding constant for FGFR1 kinase domain None 99.0 nM
Binding constant for YSK4 kinase domain None 500.0 nM
Drug metabolism in human liver microsomes assessed as 1 uM ketaconazole-mediated inhibition of CYP3A5-mediated (R)-1-(4-(4-fluoro-2-(hydroxymethyl)-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol formation at 2 and 20 uM for 30 mins by LC/MS analysis Homo sapiens 50.0 %
Inhibition of human recombinant VEGFR-2 Homo sapiens 26.0 nM
Inhibition of human recombinant FGFR-1 Homo sapiens 28.0 nM
Drug metabolism in human liver microsomes assessed as monoclonal antibody-mediated inhibition of CYP1A2-mediated (R)-1-(4-(4-fluoro-2-(hydroxymethyl)-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol formation at 2 and 20 uM for 30 mins by LC/MS analysis Homo sapiens 55.0 %
Drug metabolism in human liver microsomes assessed as monoclonal antibody-mediated inhibition of CYP3A4-mediated (R)-1-(4-(4-fluoro-2-(hydroxymethyl)-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol formation at 2 and 20 uM for 30 mins by LC/MS analysis Homo sapiens 50.0 %
Drug metabolism in human liver microsomes assessed as monoclonal antibody-mediated inhibition of CYP3A5-mediated (R)-1-(4-(4-fluoro-2-(hydroxymethyl)-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol formation at 2 and 20 uM for 30 mins by LC/MS analysis Homo sapiens 50.0 %
Inhibition of recombinant VEGFR-2 (unknown origin) Homo sapiens 26.0 nM
Inhibition of recombinant FGFR-1 (unknown origin) Homo sapiens 28.0 nM
Inhibition of VEGF-stimulated HUVEC cell proliferation assessed as 5-bromo-2-deoxyuridine incorporation Homo sapiens 618.0 nM
Inhibition of FGF-stimulated HUVEC cell proliferation assessed as 5-bromo-2-deoxyuridine incorporation Homo sapiens 695.0 nM
Inhibition of VEGF/FGF-stimulated HUVEC cell proliferation assessed as 5-bromo-2-deoxyuridine incorporation Homo sapiens 841.0 nM
Drug metabolism in human liver microsomes assessed as 1 mM 1-ABT-mediated inhibition of P450-mediated (R)-1-(4-(4-fluoro-2-(hydroxymethyl)-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol formation at 2 and 20 uM for 30 mins by LC/MS analysis relative to control Homo sapiens 95.0 %
Drug metabolism in human liver microsomes assessed as 10 uM furafylline-mediated inhibition of CYP1A2-mediated (R)-1-(4-(4-fluoro-2-(hydroxymethyl)-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol formation at 2 and 20 uM for 30 mins by LC/MS analysis Homo sapiens 60.0 %
Drug metabolism in human liver microsomes assessed as 1 uM ketaconazole-mediated inhibition of CYP3A4-mediated (R)-1-(4-(4-fluoro-2-(hydroxymethyl)-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol formation at 2 and 20 uM for 30 mins by LC/MS analysis Homo sapiens 50.0 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 14.07 %
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 8.01 % 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 8.01 %

Related Entries

Cross References

Resources Reference
ChEBI 94562
ChEMBL CHEMBL377300
DrugBank DB11958
FDA SRS DDU33B674I
Guide to Pharmacology 5671
PubChem 11234052
SureChEMBL SCHEMBL1227589
ZINC ZINC000013684256
CONTENTS