ALPELISIB

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Trade Names
Synonyms
Status
Molecule Category UNKNOWN
ATC L01EM03
UNII 08W5N2C97Q
EPA CompTox DTXSID70153355

Structure

InChI Key STUWGJZDJHPWGZ-LBPRGKRZSA-N
Smiles Cc1nc(NC(=O)N2CCC[C@H]2C(N)=O)sc1-c1ccnc(C(C)(C)C(F)(F)F)c1
InChI
InChI=1S/C19H22F3N5O2S/c1-10-14(11-6-7-24-13(9-11)18(2,3)19(20,21)22)30-16(25-10)26-17(29)27-8-4-5-12(27)15(23)28/h6-7,9,12H,4-5,8H2,1-3H3,(H2,23,28)(H,25,26,29)/t12-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C19H22F3N5O2S
Molecular Weight 441.48
AlogP 3.84
Hydrogen Bond Acceptor 5.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 4.0
Polar Surface Area 101.21
Molecular species NEUTRAL
Aromatic Rings 2.0
Heavy Atoms 30.0

Bioactivity

Mechanism of Action Action Reference
PI3-kinase p110-alpha subunit inhibitor INHIBITOR PubMed PubMed
Protein: PI3-kinase p110-alpha subunit
Description: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Organism : Homo sapiens
P42336 ENSG00000121879
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
- 1461-3000 - - -
Enzyme Transferase
- 5-200 - - -
Enzyme
- 5-200 - - -
Assay Description Organism Bioactivity Reference
Inhibition of N-terminal myristoylated P110alpha (unknown origin)-mediated AKT phosphorylation at Ser473 expressed in rat Rat1 cells by ELISA Homo sapiens 74.0 nM
Inhibition of P110gamma (unknown origin) using PIP2:PS as substrate by TR-FRET assay Homo sapiens 250.0 nM
Inhibition of P110delta (unknown origin) using PIP2:PS as substrate by TR-FRET assay Homo sapiens 290.0 nM
Inhibition of P110alpha (unknown origin) using L-a-phosphatidylinositol as substrate by luminescence assay Homo sapiens 5.0 nM
Inhibition of P110alpha (unknown origin) by Kinase-Glo assay Homo sapiens 5.0 nM
Inhibition of P110gamma (unknown origin) using PI or PIP2:PS as substrate measured for 15 to 60 mins by TR-FRET analysis Homo sapiens 250.0 nM
Inhibition of P110delta (unknown origin) using PI or PIP2:PS as substrate measured for 15 to 60 mins by TR-FRET analysis Homo sapiens 290.0 nM
Inhibition of myristoylated human P110alpha expressed in Rat1 cells assessed as inhibition of Akt phosphorylation at Serine 473 by Western blot analysis Homo sapiens 74.0 nM
Inhibition of PI3Kalpha (unknown origin) Homo sapiens 5.0 nM
Inhibition of PI3Kgamma (unknown origin) Homo sapiens 250.0 nM
Inhibition of PI3Kdelta (unknown origin) Homo sapiens 290.0 nM
Inhibition of PI3Kalpha in rat Rat1 cells assessed as reduction of Akt phosphorylation at Ser473 in presence of 0.5% fetal calf serum Rattus norvegicus 74.0 nM
Inhibition of recombinant PI3Kalpha (unknown origin) by KinaseGlo assay Homo sapiens 4.6 nM
Inhibition of P13Kalpha (unknown origin) Homo sapiens 5.0 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 -9.04 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 11.28 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 9.392 %
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 -0.16 % 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 -0.36 % 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 -0.36 % 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 -0.16 %
Antiproliferation activity against human T47D cells assessed as reduction in cell viability incubated for 7 days by Cell-titer Glo reagent based assay Homo sapiens 420.0 nM
Inhibition of PI3K p110alpha H1047R mutant in human T47D cells assessed as reduction in phosphorylation of Akt at T308 residue incubated for 2 hrs by ELISA Homo sapiens 30.0 nM
Inhibition of PI3K p110alpha E542K mutant in human MCF7 cells assessed as reduction in phosphorylation of Akt at T308 residue incubated for 2 hrs by ELISA Homo sapiens 39.0 nM
Antiproliferation activity against human MCF7 cells assessed as reduction in cell viability incubated for 7 days by Cell-titer Glo reagent based assay Homo sapiens 530.0 nM
Inhibition of recombinant human N-terminal Myr signal and C-terminal Flag-tagged PI3K p110delta expressed in rat Rat1 cells Homo sapiens 510.0 nM
Inhibition of recombinant human N-terminal Myr signal and C-terminal Flag-tagged PI3K p110alpha expressed in rat Rat1 cells Homo sapiens 200.0 nM
Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate measured after 1 hr by ADP-glo plus luminescence assay Homo sapiens 139.0 nM
Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate measured after 1 hr by ADP-glo plus luminescence assay Homo sapiens 190.0 nM
Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after 1 hr by ADP-glo plus luminescence assay Homo sapiens 9.5 nM
Inhibition of PI3Kalpha (unknown origin) Homo sapiens 5.0 nM
Inhibition of human PI3Kalpha using PIP2 as substrate in presence of ATP measured after 30 mins by HTRF assay Homo sapiens 17.8 nM
Inhibition of human PI3K p110alpha E545K mutant/p85alpha using PIP2 as substrate incubated for 40 mins in presence of ATP by HTRF assay Homo sapiens 18.9 nM
Inhibition of human PI3K p110alpha H1047R mutant/p85alpha using PIP2 as substrate incubated for 40 mins in presence of ATP by HTRF assay Homo sapiens 10.9 nM
Inhibition of human PI3K p110delta/p85alpha using PIP2 as substrate in presence of ATP measured after 40 mins by HTRF assay Homo sapiens 382.8 nM
Inhibition of His-tagged human full length PI3Kalpha coexpressed with p85 alpha in baculovirus expression system using PIP2 peptide as substrate incubated for 1 hr in presence ATP by Kinase-Glo assay Homo sapiens 3.9 nM
Inhibition of GST-tagged human recombinant PI3Kgamma catalytic domain (468 to 1203 residues) expressed in insect cells using PIP2 peptide as substrate incubated for 1 hr in presence ATP by ADP-Glo Kinase Assay Homo sapiens 94.0 nM
Inhibition of N-terminal His6-tagged human recombinant full length PI3Kdelta co-expressed with human recombinant full length P85alpha in baculovirus infected Sf21 cells using PIP2 peptide as substrate incubated for 2 hrs in presence ATP by ADP-Glo Kinase Assay Homo sapiens 72.0 nM

Cross References

Resources Reference
ChEBI 93752
ChEMBL CHEMBL2396661
DrugBank DB12015
DrugCentral 5328
FDA SRS 08W5N2C97Q
Guide to Pharmacology 7955
PDB 1LT
PubChem 56649450
SureChEMBL SCHEMBL1911869
ZINC ZINC000068198368
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