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Compound Detail

CHEMBL2396661

ALPELISIB
💊 Approved Drug
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💊 Approved Drug
Cc1nc(NC(=O)N2CCC[C@H]2C(N)=O)sc1-c1ccnc(C(C)(C)C(F)(F)F)c1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL2396661
Name ALPELISIB
Phase Approved
Structure Type MOL
InChI Key STUWGJZDJHPWGZ-LBPRGKRZSA-N
Therapeutic ✓ Yes

Known Names

Alpelisib Byl-719 BYL719 NVP-BYL719 Piqray Vijoice
20
Targets
80
Activities
2
Assay Types
14
PK Parameters
20
Publications
6
Known Names
20
Indications
1
Mechanisms

Molecular Properties

441.5
MW (Da)
3.84
ALogP
5
HBA
2
HBD
101.2
PSA (Ų)
0.75
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2019
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Chemical Probe
USAN Stem -lisib
USAN Year 2016

Extended Properties

Molecular Formula C19H22F3N5O2S
MW 441.48
Aromatic Rings 2
Heavy Atoms 30
NP-Likeness -1.46

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
PI3-kinase p110-alpha subunit inhibitor INHIBITOR Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform ✓ ✓

Indications

Breast Neoplasms Breast Neoplasms Breast Neoplasms Neoplasms Neoplasms Carcinoma, Squamous Cell Carcinoma, Squamous Cell Colorectal Neoplasms Endometrial Neoplasms Head and Neck Neoplasms Lymphedema Ovarian Neoplasms Squamous Cell Carcinoma of Head and Neck Triple Negative Breast Neoplasms Esophageal Neoplasms Gastrointestinal Stromal Tumors Liver Diseases Meningioma Multiple Myeloma Oropharyngeal Neoplasms

ATC Classification

L01EM03
alpelisib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 78 meas. best 8.77
Kd 2 meas. best 5.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL4005
 IC50 8.77 8.04 1.7 20
PI3-kinase p110-alpha/p85-alpha
CHEMBL2111367
 IC50 8.41 8.41 3.9 1
Unchecked
CHEMBL612545
 IC50 7.96 6.8625 10.9 8
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
 IC50 7.16 6.393 69.0 10
PI3-kinase p110-delta/p85-alpha
CHEMBL2111432
 IC50 7.14 6.78 72.0 2
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
 IC50 7.03 6.735 94.0 8
T47D
CHEMBL614361
 IC50 7.0 6.355 100.0 4
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
 IC50 6.72 5.9033 190.0 9
MV4-11
CHEMBL613835
 IC50 6.72 6.09 190.0 2
MCF7
CHEMBL387
 IC50 6.6 6.3675 250.0 4
L-363
CHEMBL2366267
 IC50 6.58 6.58 260.0 1
MGC-803
CHEMBL3706566
 IC50 6.37 6.37 430.0 1
Kasumi 1
CHEMBL613988
 IC50 6.36 6.36 440.0 1
Serine/threonine-protein kinase mTOR
CHEMBL2842
 IC50 5.83 5.675 1461.0 2
PI3K p110 beta/p85 alpha
CHEMBL3038510
 IC50 5.81 5.775 1540.0 2
cAMP-dependent protein kinase catalytic subunit gamma
CHEMBL2743
 Kd 5.7 5.7 1990.0 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3608198
 IC50 5.66 5.66 2200.0 1
Cyclin-G-associated kinase
CHEMBL4355
 Kd 5.3 5.3 4968.0 1
SJRH30
CHEMBL1075575
 IC50 5.12 5.12 7600.0 1
MDA-MB-231
CHEMBL400
 IC50 4.2 4.2 62900.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 8.0 mL.min-1.kg-1 Canis lupus familiaris
CL 10.0 mL.min-1.kg-1 Rattus norvegicus
CL 8.0 mL.min-1.kg-1 Mus musculus
CL 10.0 mL.min-1.kg-1 Rattus norvegicus
CL 29.0 mL.min-1.g-1 Rattus norvegicus
CL 29.0 mL.min-1.g-1 Rattus norvegicus
CL 29.0 mL.min-1.g-1 Rattus norvegicus
Cmax 1070.0 nM Canis lupus familiaris
Cmax 190.0 nM Rattus norvegicus
Cmax 520.0 nM Mus musculus
F 140.0 % Canis lupus familiaris
F 58.0 % Rattus norvegicus
F 106.0 % Mus musculus
T1/2 2.9 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 1.7 nM 8.77 Inhibition of PI3Kalpha (unknown origin) incubated for 60 mins in presence of AT... 39159497
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 3.0 nM 8.52 Inhibition of PI3Kalpha H1047R mutant (unknown origin) using PI(4,5)P2:PS as sub... 38477582
PI3-kinase p110-alpha/p85-alpha IC50 = 3.9 nM 8.41 Inhibition of His-tagged human full length PI3Kalpha coexpressed with p85 alpha ... 32375077
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 4.6 nM 8.34 Inhibition of recombinant PI3Kalpha (unknown origin) by KinaseGlo assay 27644332
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 4.6 nM 8.34 Inhibition of wild type PI3Kalpha (unknown origin) 38477582
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 4.6 nM 8.34 Inhibition of PI3Kalpha (unknown origin) 37736169
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 4.8 nM 8.32 Inhibition of PI3Kalpha H1047R mutant (unknown origin) 38477582
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 5.0 nM 8.3 Inhibition of P13Kalpha (unknown origin) 28341403
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 5.0 nM 8.3 Inhibition of P110alpha (unknown origin) using L-a-phosphatidylinositol as subst... 23726034
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 5.0 nM 8.3 Inhibition of P110alpha (unknown origin) by Kinase-Glo assay 26164189
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 5.0 nM 8.3 Inhibition of PI3Kalpha (unknown origin) 26206504
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 5.0 nM 8.3 Inhibition of PI3Kalpha (unknown origin) 33214824
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 5.0 nM 8.3 Affinity Biochemical interaction (Enzymatic inhibition assay (Kinase-Glo® assay)... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 5.0 nM 8.3 Inhibition of PI3K alpha (unknown origin) 37652098
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 6.1 nM 8.21 Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1... 38048697
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 9.5 nM 8.02 Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after ... 33199203
Unchecked IC50 = 10.9 nM 7.96 Inhibition of human PI3K p110alpha H1047R mutant/p85alpha using PIP2 as substrat... 33109399
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 17.8 nM 7.75 Inhibition of human PI3Kalpha using PIP2 as substrate in presence of ATP measure... 33109399
Unchecked IC50 = 18.9 nM 7.72 Inhibition of human PI3K p110alpha E545K mutant/p85alpha using PIP2 as substrate... 33109399
Unchecked IC50 = 30.0 nM 7.52 Inhibition of PI3K p110alpha H1047R mutant in human T47D cells assessed as reduc... 33356246

Literature References

PubMed DOI Target Context # Activities
39159497 10.1021/acs.jmedchem.4c00992 MCF7 14
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL4689842 U2OS 9
- 10.6019/CHEMBL4689842 Fibroblast 9
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
- 10.6019/CHEMBL4689842 HEK-293T 6
23726034 10.1016/j.bmcl.2013.05.007 Rattus norvegicus 6
33356246 10.1021/acs.jmedchem.0c01652 Unchecked 5
29191878 10.1126/science.aan4368 Unchecked 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
23726034 10.1016/j.bmcl.2013.05.007 Mus musculus 3
23726034 10.1016/j.bmcl.2013.05.007 Canis familiaris 3
39159497 10.1021/acs.jmedchem.4c00992 Unchecked 3
38048697 10.1016/j.ejmech.2023.116015 MV4-11 3
33109399 10.1016/j.ejmech.2020.112913 Unchecked 3
26164189 10.1016/j.bmcl.2015.06.077 Unchecked 3
38477582 10.1021/acs.jmedchem.4c00078 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 3
23726034 10.1016/j.bmcl.2013.05.007 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 2
23726034 10.1016/j.bmcl.2013.05.007 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 2

Data from ChEMBL 36 via Core Engine