BGT-226

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Synonyms
Status
Molecule Category Mixture
UNII ZXE7F2GMJJ
EPA CompTox DTXSID60238600

Structure

InChI Key BMMXYEBLEBULND-UHFFFAOYSA-N
Smiles COc1ccc(-c2ccc3ncc4c(c3c2)n(-c2ccc(N3CCNCC3)c(C(F)(F)F)c2)c(=O)n4C)cn1
InChI
InChI=1S/C28H25F3N6O2/c1-35-24-16-33-22-6-3-17(18-4-8-25(39-2)34-15-18)13-20(22)26(24)37(27(35)38)19-5-7-23(21(14-19)28(29,30)31)36-11-9-32-10-12-36/h3-8,13-16,32H,9-12H2,1-2H3

Physicochemical Descriptors

Property Name Value
Molecular Formula C28H25F3N6O2
Molecular Weight 534.54
AlogP 4.38
Hydrogen Bond Acceptor 8.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 4.0
Polar Surface Area 77.21
Molecular species BASE
Aromatic Rings 5.0
Heavy Atoms 39.0

Bioactivity

Mechanism of Action Action Reference
PI3-kinase class I inhibitor INHIBITOR PubMed PubMed
Protein: PI3-kinase class I
Description: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Organism : Homo sapiens
O00329 ENSG00000171608
Protein: PI3-kinase class I
Description: Phosphatidylinositol 3-kinase regulatory subunit beta
Organism : Homo sapiens
O00459 ENSG00000105647
Protein: PI3-kinase class I
Description: Phosphatidylinositol 3-kinase regulatory subunit alpha
Organism : Homo sapiens
P27986 ENSG00000145675
Protein: PI3-kinase class I
Description: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Organism : Homo sapiens
P42336 ENSG00000121879
Protein: PI3-kinase class I
Description: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
Organism : Homo sapiens
P42338 ENSG00000051382
Protein: Serine/threonine-protein kinase mTOR
Description: Serine/threonine-protein kinase mTOR
Organism : Homo sapiens
P42345 ENSG00000198793
Protein: PI3-kinase class I
Description: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Organism : Homo sapiens
P48736 ENSG00000105851
Protein: PI3-kinase class I
Description: Phosphoinositide 3-kinase regulatory subunit 5
Organism : Homo sapiens
Q8WYR1 ENSG00000141506
Protein: PI3-kinase class I
Description: Phosphatidylinositol 3-kinase regulatory subunit gamma
Organism : Homo sapiens
Q92569 ENSG00000117461
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Transferase
- 38 - - -
Assay Description Organism Bioactivity Reference
PIK3alpha Activity Assay: 1. Preparation of test reagents{circle around (1)} 1x kinase buffer (50 mM HEPES, pH 7.5, 3 mM MgCl2, 1 mM EGTA, 100 mM NaCl, 0.03% CHAPS, 2 mM DTT);{circle around (2)} 4x kinase solution (added PI3K a kinase to 1x kinase buffer to provide 4x kinase solution with a final concentration of 1.65 nM);{circle around (3)} 2x substrate solution (added the substrates of PIP2 and ATP into 1x kinase buffer to provide 2x substrate solution with PIP2 final concentration of 50 uM and ATP final concentration of 25 uM);{circle around (4)} 4x test substance solutions (100x test substance solutions with different concentration gradients were prepared using 100% DMSO, and diluted 25-fold with 1x kinase buffer to give 4x test substance solutions with different concentration gradients);{circle around (5)} Invitrogen's activity test kit with the test solution was kept stand to room temperature. 2. 2.5 uL of 4x test solution was added to a 384-well plate in parallel; 3. added 2.54 uL of 4x kinase solution and incubated for 10 min; 4. then added 5 uL of 2x solutions of PIP2 and ATP substrates and incubated for 1 h at room temperature; 5. finally, added 10 uL of test solution to quench the reaction, and read after 15 min; 6. IC50 value was obtained via curve fitting. Inhibition rate (%)=(sample value-minimum)/(maximum-minimum)x100. Homo sapiens 41.91 nM
mTOR Activity Assay: 1. Preparation of test reagents {circle around (1)} 1x kinase buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM EGTA, 3 mM MnCl, 0.01% Tween-20, 2 mM DTT); {circle around (2)} 4x kinase solution (added mTOR kinase to 1x kinase buffer to provide 4x kinase solution with a final concentration of 2.5 nM); {circle around (3)} 2x substrate solution (added the substrates of 4EBP1 and ATP into 1x kinase buffer to provide 2x substrate solution with 4EBP1 final concentration of 50 nM and ATP final concentration of 10.8 uM); {circle around (4)} 4x test substance solutions (100x test substance solutions with different concentration gradients were prepared using 100% DMSO, and diluted 25-fold with 1x kinase buffer to give 4x test substance solutions with different concentration gradients) {circle around (5)} preparation of test solution (test solution containing EDTA and 4EBP1 phosphorylated antibody was prepared using activity test kit with assay buffer, the final concentration of EDTA was 8 mM, and the final concentration of 4EBP1 phosphorylated antibody was 2 nM) 2. 2.5 uL of 4x test solution was added to a 384-well plate in parallel; 3. added 2.54 uL of 4x kinase solution and incubated for 10 min; 4. then added 5 uL of 2x solutions of 4EBP1 and ATP substrates and incubated for 1 h at room temperature; 5. finally, added 10 uL of test solution to quench the reaction, and read after 60 min; 6. IC50 value was obtained via curve fitting. Homo sapiens 1.99 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 246.0 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 922.0 nM
Inhibition of PI3Kalpha (unknown origin) Homo sapiens 4.0 nM
Inhibition of PI3Kbeta (unknown origin) Homo sapiens 63.0 nM
Inhibition of PI3Kgamma (unknown origin) Homo sapiens 38.0 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 -3.69 %
Antiparasitic activity against bloodstream form of Trypanosoma brucei 221 infected in mouse VSMC assessed as reduction in parasitic proliferation after 48 hrs by cell titer-glo based assay Trypanosoma brucei 950.0 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 -2.525 %
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 -0.22 % 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 -0.22 %

Cross References

Resources Reference
ChEBI 71967
ChEMBL CHEMBL3218578
FDA SRS ZXE7F2GMJJ
Guide to Pharmacology 7951
SureChEMBL SCHEMBL146939
ZINC ZINC000073069304
ChEBI 71953
ChEMBL CHEMBL3545096
FDA SRS 4YG62LG876
SureChEMBL SCHEMBL996046
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