LENIOLISIB

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Synonyms
Status
Molecule Category UNKNOWN
UNII L22772Z9CP

Structure

InChI Key MWKYMZXCGYXLPL-ZDUSSCGKSA-N
Smiles CCC(=O)N1CC[C@H](Nc2ncnc3c2CN(c2cnc(OC)c(C(F)(F)F)c2)CC3)C1
InChI
InChI=1S/C21H25F3N6O2/c1-3-18(31)30-6-4-13(10-30)28-19-15-11-29(7-5-17(15)26-12-27-19)14-8-16(21(22,23)24)20(32-2)25-9-14/h8-9,12-13H,3-7,10-11H2,1-2H3,(H,26,27,28)/t13-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C21H25F3N6O2
Molecular Weight 450.47
AlogP 2.88
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 5.0
Polar Surface Area 83.48
Molecular species NEUTRAL
Aromatic Rings 2.0
Heavy Atoms 32.0

Bioactivity

Mechanism of Action Action Reference
PI3-kinase p110-delta subunit inhibitor INHIBITOR PubMed PubMed
Protein: PI3-kinase p110-delta subunit
Description: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Organism : Homo sapiens
O00329 ENSG00000171608
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase AGC protein kinase group AGC protein kinase RSK family AGC protein kinase MSK subfamily
- - - - 76
Enzyme Kinase Protein Kinase Atypical protein kinase group Atypical protein kinase PIKK family
- 880 - - -
Enzyme Kinase Protein Kinase CAMK protein kinase group CAMK protein kinase RSKb family CAMK protein kinase MSKb subfamily
- - - - 76
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4D
- 4700 - - -
Enzyme Transferase
- 11-1150 - - -
Membrane receptor Family A G protein-coupled receptor Small molecule receptor (family A GPCR) Monoamine receptor Serotonin receptor
- 7700 - - -
Assay Description Organism Bioactivity Reference
Enzyme Assay: Test of Lipid Kinase Activity: The kinase reaction is performed in a final volume of 50 μl per well of a half area COSTAR, 96 well plate. The final concentrations of ATP and phosphatidyl inositol in the assay are 5 μM and 6 μg/mL, respectively. The reaction is started by the addition of PI3 kinase, e.g. PI3 kinase δ. Refer to the patent for more info. Homo sapiens 262.0 nM
Enzyme Assay: Test of Lipid Kinase Activity: The kinase reaction is performed in a final volume of 50 μl per well of a half area COSTAR, 96 well plate. The final concentrations of ATP and phosphatidyl inositol in the assay are 5 μM and 6 μg/mL, respectively. The reaction is started by the addition of PI3 kinase, e.g. PI3 kinase δ. Refer to the patent for more info. Homo sapiens 23.0 nM
Inhibition of recombinant PI3Kalpha (unknown origin) using phosphatidyl inositol/n-Octyl-glucoside as substrate measured after 30 mins by KinaseGlo assay Homo sapiens 244.0 nM
Inhibition of recombinant PI3Kbeta (unknown origin) using phosphatidyl inositol/n-Octyl-glucoside as substrate measured after 60 mins by KinaseGlo assay Homo sapiens 424.0 nM
Inhibition of PI3Kdelta (unknown origin) using phosphatidyl inositol as substrate measured after 60 mins by Alexa Fluor647-labelled ADP tracer based TR-FRET assay Homo sapiens 11.0 nM
Inhibition of recombinant human myristoylated PI3Kdelta catalytic domain expressed in Rat1 cells assessed as reduction in Akt phosphorylation at Ser47 residue after 1 hr by alpha screen Surefire assay Homo sapiens 56.0 nM
Inhibition of PI3Kdelta in Balb/c mouse splenocytes assessed as reduction in anti-IgM stimulated CD86 expression pretreated for 1 hr followed by anti-IgM stimulation after 24 hrs by flow cytometric analysis Mus musculus 48.0 nM
Inhibition of PI3Kdelta in 50% rat blood assessed as reduction in anti-IgM stimulated CD86 expression pretreated for 1 hr followed by anti-IgM stimulation after 24 hrs by flow cytometric analysis Rattus norvegicus 99.0 nM
Inhibition of PI3Kdelta in mouse B cells assessed as reduction in anti-IgM-induced cell proliferation measured last 16 hrs of 88 hrs incubation by [3H]thymidine incorporation assay Mus musculus 7.0 nM
Inhibition of PI3Kdelta in human B cells assessed as reduction in anti-IgM-induced AKT phosphorylation at ser473 residue pretreated for 1.5 hrs followed by anti-IgM stimulation after 20 mins by flow cytometric analysis Homo sapiens 144.0 nM
Inhibition of PI3Kdelta in 90% human whole blood assessed as reduction in anti-IgM/IL4 stimulated CD86 expression pretreated for 1 hr followed by anti-IgM/IL4 stimulation after 24 hrs by flow cytometric analysis Homo sapiens 202.0 nM
Inhibition of PI3Kdelta in 90% human whole blood assessed as reduction in anti-IgM/IL4 stimulated CD69 expression pretreated for 1 hr followed by anti-IgM/IL4 stimulation after 24 hrs by flow cytometric analysis Homo sapiens 193.0 nM
Ex-vivo inhibition of PI3Kdelta in po dosed cynomolgus monkey assessed as reduction in anti-IgM-induced AKT phosphorylation at ser473 residue in whole blood pretreated up to 24 hrs followed by anti-IgM stimulation after 20 mins by flow cytometric analysis Macaca fascicularis 84.0 nM
Inhibition of PI3Kdelta in 50% rat blood assessed as reduction in anti-IgM stimulated AKT phosphorylation at ser473 residue pretreated for 1.5 hr followed by anti-IgM stimulation after 10 mins by flow cytometric analysis Rattus norvegicus 150.0 nM
Inhibition of PI3Kdelta in human PBMC assessed as reduction in cell proliferation by measuring [3H]thymidine incorporation measured last 16 hrs of 4 days incubation by beta counting based mixed lymphocyte reaction assay Homo sapiens 79.0 nM
Inhibition of PI3Kdelta in anti-CD3 stimulated human PBMC assessed as reduction in cell proliferation by measuring [3H]thymidine incorporation pretreated for 1 hr followed by anti-CD3 addition measured last 16 hrs of 56 hrs incubation by beta counting method Homo sapiens 159.0 nM
Inhibition of PI3Kdelta in anti-CD3/CD28 stimulated human PBMC derived CD4-positive T cells assessed as reduction in T cell differentiation to Th2 cells by measuring IL-13 level after 72 hrs by ELISA Homo sapiens 95.0 nM
Inhibition of PI3Kdelta in anti-CD3/CD28 stimulated human PBMC derived CD4-positive T cells assessed as reduction in T cell differentiation to Th17 cells by measuring IL-17A level after 72 hrs by ELISA Homo sapiens 73.0 nM
Inhibition of PI3Kdelta in mouse spleen cells assessed as reduction in cell proliferation by measuring [3H]thymidine incorporation by beta counting based mixed lymphocyte reaction assay Mus musculus 33.0 nM
Inhibition of PI3Kdelta in anti-CD3/CD28 stimulated mouse CD4-positive T cells assessed as reduction in T cell differentiation to Th2 cells by measuring IL-13 level after 72 hrs by ELISA Mus musculus 10.0 nM
Inhibition of PI3Kdelta in anti-CD3/CD28 stimulated mouse CD4-positive T cells assessed as reduction in T cell differentiation to Th17 cells by measuring IL-17A level after 72 hrs by ELISA Mus musculus 101.0 nM
Inhibition of DNA-PK (unknown origin) using peptide substrate assessed as reduction in incorporation of radioactive 33p into substrate by liquid scintillation counting method Homo sapiens 880.0 nM
Inhibition of wild-type human partial length RPS6KA5 expressed in bacterial expression system at 10 uM by Kinomescan method relative to control Homo sapiens 76.0 %
Ex-vivo inhibition of PI3Kdelta in po dosed Lewis rat assessed as reduction in anti-IgM/IL4-induced AKT phosphorylation at ser473 residue in whole blood pretreated up to 24 hrs followed by anti-IgM/IL4 stimulation after 10 mins by flow cytometric analysis Rattus norvegicus 83.0 nM
In-vivo inhibition of PI3Kdelta in sheep RBC-sensitized OFA-rat assessed as reduction in antigen-specific antibody response to SRBC by measuring plaque formation at 3 mg/kg, po bid treated for 4 days starting from day 1 of immunization by microscopic method relative to control Rattus norvegicus 54.0 %
In-vivo inhibition of PI3Kdelta in sheep RBC-sensitized OFA-rat assessed as reduction in antigen-specific antibody response to SRBC by measuring plaque formation at 10 mg/kg, po bid treated for 4 days starting from day 1 of immunization by microscopic method relative to control Rattus norvegicus 73.0 %
In-vivo inhibition of PI3Kdelta in sheep RBC-sensitized OFA-rat assessed as reduction in antigen-specific antibody response to SRBC by measuring plaque formation at 30 mg/kg, po bid treated for 4 days starting from day 1 of immunization by microscopic method relative to control Rattus norvegicus 96.0 %

Cross References

Resources Reference
ChEMBL CHEMBL3643413
DrugBank DB16217
FDA SRS L22772Z9CP
Guide to Pharmacology 9424
PDB 9NQ
PubChem 57495353
SureChEMBL SCHEMBL323054
CONTENTS