APITOLISIB

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Synonyms
Status
Molecule Category UNKNOWN
UNII 1C854K1MIJ
EPA CompTox DTXSID50145738

Structure

InChI Key YOVVNQKCSKSHKT-HNNXBMFYSA-N
Smiles Cc1c(CN2CCN(C(=O)[C@H](C)O)CC2)sc2c(N3CCOCC3)nc(-c3cnc(N)nc3)nc12
InChI
InChI=1S/C23H30N8O3S/c1-14-17(13-29-3-5-31(6-4-29)22(33)15(2)32)35-19-18(14)27-20(16-11-25-23(24)26-12-16)28-21(19)30-7-9-34-10-8-30/h11-12,15,32H,3-10,13H2,1-2H3,(H2,24,25,26)/t15-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C23H30N8O3S
Molecular Weight 498.61
AlogP 0.9
Hydrogen Bond Acceptor 11.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 5.0
Polar Surface Area 133.83
Molecular species NEUTRAL
Aromatic Rings 3.0
Heavy Atoms 35.0

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 Kinase Protein Kinase Atypical protein kinase group Atypical protein kinase PIKK family Atypical protein kinase FRAP subfamily
- - 3 17-17 -
Enzyme Kinase Protein Kinase Atypical protein kinase group Atypical protein kinase PIKK family
- - 3 17-17 -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Src family
- 697 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Syk family
- 134 - - -
Enzyme Kinase Protein Kinase TKL protein kinase group TKL protein kinase MLK family TKL protein kinase MLK subfamily
- 232 - - -
Enzyme Transferase
- 14-36 1 5 -
Assay Description Organism Bioactivity Reference
Inhibition of PI3K subunit p110alpha assessed as formation of phosphatidylinositide-3-phosphate product formation after 30 mins by fluorescence polarization assay None 4.8 nM
Inhibition of human recombinant mTOR expressed in insect cells assessed as phosphorylation of recombinant (GFP)-4-EBP1 measured after 30 mins by fluorescence polarization assay Homo sapiens 17.0 nM
Inhibition of PI3K subunit p110beta assessed as formation of phosphatidylinositide-3-phosphate product formation after 30 mins by fluorescence polarization assay None 27.0 nM
Inhibition of PI3K subunit p110delta assessed as formation of phosphatidylinositide-3-phosphate product formation after 30 mins by fluorescence polarization assay None 6.7 nM
Inhibition of PI3K subunit p110gamma assessed as formation of phosphatidylinositide-3-phosphate product formation after 30 mins by fluorescence polarization assay None 14.0 nM
Antiproliferative activity against human PC3 cells after overnight incubation by CellTiter-Glo luminescence assay Homo sapiens 307.0 nM
Antiproliferative activity against human MCF7.1 cells expressing HER2 gene after overnight incubation by CellTiter-Glo luminescence assay Homo sapiens 255.0 nM
Inhibition of PIK3 gamma-mediated Akt phosphorylation at Ser473 in human PC3 cells by ELISA Homo sapiens 36.0 nM
Inhibition of Fgr at 1 uM None 60.0 %
Inhibition of Mlk1 at 1 uM None 60.0 %
Inhibition of PAK4 at 1 uM None 60.0 %
Inhibition of Syk at 1 uM None 60.0 %
Inhibition of Yes1 at 1 uM None 60.0 %
Inhibition of Fgr None 697.0 nM
Inhibition of Mlk1 None 232.0 nM
Inhibition of Syk None 134.0 nM
Inhibition of PIKKC2beta by scintillation proximity assay None 794.0 nM
Inhibition of DNA-PK using 5-FAM-AEPPLSQEAFADLWKK-NH2 as substrate after 60 mins by electrophoretic analysis None 623.0 nM
Inhibition of PI3Kbeta (unknown origin) Homo sapiens 27.0 nM
Inhibition of PI3Kalpha (unknown origin) Homo sapiens 5.0 nM
Inhibition of PI3Kgamma (unknown origin) Homo sapiens 14.0 nM
Inhibition of PI3Kdelta (unknown origin) Homo sapiens 7.0 nM
Inhibition of mTOR (unknown origin) Homo sapiens 17.0 nM
Inhibition of recombinant PI3Kalpha (unknown origin) using dioctanoylglycerol-PIP2 as substrate incubated for 30 mins in presence of TAMRA-PIP3 by fluorescence polarization assay Homo sapiens 5.0 nM
Inhibition of human recombinant mTOR (1360 to 2549 residues) expressed in insect cells assessed as inhibition of GFP-labeled 4-EBP1 phosphorylation at Thr-37/46 residues incubated for 30 mins by FRET assay Homo sapiens 17.0 nM
Antiproliferative activity against human PC3 cells after 3 days by CellTitre-Glo assay Homo sapiens 310.0 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 814.0 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 26.0 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 904.0 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 570.0 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 721.0 nM
Binding affinity to human PI3Kalpha (R108 to N1068 residues) expressed in mammalian expression system by Kinomescan assay Homo sapiens 0.62 nM
Binding affinity to human PI3Kbeta (P118 to S1070 residues) expressed in mammalian expression system by Kinomescan assay Homo sapiens 3.8 nM
Binding affinity to human PI3Kgamma (S144 to A1102 residues) expressed in mammalian expression system by Kinomescan assay Homo sapiens 2.6 nM
Binding affinity to human PI3Kdelta (R108 to Q1044 residues) expressed in mammalian expression system by Kinomescan assay Homo sapiens 3.3 nM
Binding affinity to human mTOR (L1382 to W2549 residues) expressed in mammalian expression system at 10 uM Homo sapiens 3.3 nM
Binding affinity to human PI3KC2beta (M1 to L1634 residues) expressed in mammalian expression system by Kinomescan assay Homo sapiens 580.0 nM
Binding affinity to human VPS34 (S282 to H879 residues) expressed in mammalian expression system by Kinomescan assay Homo sapiens 250.0 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 101.92 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 9.82 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -7.568 %
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 12.58 % 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 6.67 % 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 12.58 % 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 6.67 %
Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after 40 mins by ADP-glo plus luminescence assay Homo sapiens 5.0 nM

Cross References

Resources Reference
ChEMBL CHEMBL1922094
DrugBank DB12180
FDA SRS 1C854K1MIJ
Guide to Pharmacology 7888
PDB 980
PubChem 25254071
SureChEMBL SCHEMBL466297
ZINC ZINC000059224388
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