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Compound Detail

CHEMBL592445

GEDATOLISIB
🧪 Phase III
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🧪 Phase III
CN(C)C1CCN(C(=O)c2ccc(NC(=O)Nc3ccc(-c4nc(N5CCOCC5)nc(N5CCOCC5)n4)cc3)cc2)CC1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL592445
Name GEDATOLISIB
Phase Phase III
Structure Type MOL
InChI Key DWZAEMINVBZMHQ-UHFFFAOYSA-N

Known Names

Gedatolisib PF-05212384 PKI-587
21
Targets
63
Activities
2
Assay Types
23
PK Parameters
20
Publications
3
Known Names
7
Indications
2
Mechanisms

Molecular Properties

615.7
MW (Da)
3.02
ALogP
10
HBA
2
HBD
128.3
PSA (Ų)
0.41
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Natural Product
USAN Stem -lisib
USAN Year 2013

Extended Properties

Molecular Formula C32H41N9O4
MW 615.74
Aromatic Rings 3
Heavy Atoms 45
NP-Likeness -1.44

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine/threonine-protein kinase mTOR inhibitor INHIBITOR Serine/threonine-protein kinase mTOR ✓ ✓
PI3-kinase class I inhibitor INHIBITOR PI3-kinase class I ✓ ✓

Indications

Breast Neoplasms Endometrial Neoplasms Leukemia, Myeloid, Acute Myelodysplastic Syndromes Carcinoma, Non-Small-Cell Lung Neoplasms Neoplasms

Activity Summary

IC50 56 meas. best 9.4
Kd 7 meas. best 9.34

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase mTOR
CHEMBL2842
 IC50 9.4 8.9067 0.4 9
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL4005
 IC50 9.4 9.0455 0.4 11
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
CHEMBL5554
 Kd 9.34 9.34 0.5 1
Serine/threonine-protein kinase mTOR
CHEMBL2842
 Kd 9.03 9.03 0.9 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL4005
 Kd 9.0 9.0 1.0 1
MDA-MB-361
CHEMBL614129
 IC50 8.52 8.46 3.0 2
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
 Kd 8.46 8.46 3.5 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
 IC50 8.27 7.9133 5.4 6
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
 IC50 8.22 7.485 6.0 4
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
 IC50 8.22 7.89 6.0 4
Unchecked
CHEMBL612545
 IC50 8.1 8.1 8.0 1
PC-3
CHEMBL390
 IC50 7.96 7.96 11.0 1
NON-PROTEIN TARGET
CHEMBL3879801
 IC50 7.88 7.88 13.1 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
 Kd 7.62 7.62 24.0 1
A-431
CHEMBL614069
 IC50 7.22 7.22 60.0 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
 Kd 7.12 7.12 76.0 1
BaF3
CHEMBL614524
 IC50 7.0 7.0 100.0 1
NCI-H1975
CHEMBL614348
 IC50 6.94 6.94 115.0 1
CNE-2
CHEMBL4296409
 IC50 6.7 6.115 200.0 2
MCF7
CHEMBL387
 IC50 6.43 6.13 370.0 2
HCT-116
CHEMBL394
 IC50 6.29 6.15 510.0 2
MDA-MB-231
CHEMBL400
 IC50 5.97 5.79 1080.0 2
HeLa
CHEMBL399
 IC50 5.97 5.615 1070.0 2
HepG2
CHEMBL395
 IC50 5.44 5.135 3600.0 2
L02
CHEMBL4296457
 IC50 5.36 4.96 4380.0 2
Phosphatidylinositol 3-kinase catalytic subunit type 3
CHEMBL1075165
 Kd 5.29 5.29 5100.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 42593.0 ng.hr.mL-1 Mus musculus
AUC 57927.0 ng.hr.mL-1 Mus musculus
AUC 41824.0 ng.hr.mL-1 Rattus norvegicus
AUC 42154.0 ng.hr.mL-1 Rattus norvegicus
AUC 5277.0 ng.hr.mL-1 Mus musculus
AUC 31526.0 ng.hr.mL-1 Mus musculus
AUC 5643.0 ng.hr.mL-1 Mus musculus
AUC 32086.0 ng.hr.mL-1 Mus musculus
CL 7.0 mL.min-1.kg-1 Mus musculus
CL 7.9 mL.min-1.kg-1 Rattus norvegicus
Cmax 17426.19 nM Mus musculus
Cmax 71491.21 nM Mus musculus
MRT 16.7 hr Mus musculus
MRT 9.1 hr Rattus norvegicus
T1/2 14.4 hr Mus musculus
T1/2 0.5 hr Homo sapiens
T1/2 0.5 hr Mus musculus
T1/2 0.5 hr Rattus norvegicus
T1/2 3.5 hr Mus musculus
T1/2 15.0 hr Rattus norvegicus
T1/2 1.3 hr Mus musculus
T1/2 7.4 hr Mus musculus
Tmax 0.03 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 = 0.4 nM 9.4 Inhibition of human PI3Kalpha expressed in SF9 insect cells after 2 hrs by fluor... 21763134
Serine/threonine-protein kinase mTOR IC50 = 0.4 nM 9.4 Inhibition of mTOR 21763134
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.4 nM 9.4 Inhibition of PI3Kalpha (unknown origin) -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.4 nM 9.4 Inhibition of wild type human PI3K p110alpha using PIP2 as substrate by TR-FRET ... 29211480
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.4 nM 9.4 Inhibition of PI3Kalpha (unknown origin) expressed in baculovirus expression sys... 34894440
Serine/threonine-protein kinase mTOR IC50 = 0.4 nM 9.4 Inhibition of mTOR (unknown origin) by lanthascreen kinase assay 38295689
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.4 nM 9.4 Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after ... 38183777
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.4 nM 9.4 Inhibition of PI3Kalpha 20166697
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta Kd = 0.46 nM 9.34 Binding affinity to human PI3KC2beta (M1 to L1634 residues) expressed in mammali... 28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.6 nM 9.22 Inhibition of PI3Kalpha E545K mutant 20166697
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 0.6 nM 9.22 Inhibition of PI3Kalpha H1047R mutant 20166697
Serine/threonine-protein kinase mTOR Kd = 0.94 nM 9.03 Binding affinity to human mTOR (L1382 to W2549 residues) expressed in mammalian ... 28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kd = 1.0 nM 9.0 Binding affinity to human PI3Kalpha (R108 to N1068 residues) expressed in mammal... 28829592
Serine/threonine-protein kinase mTOR IC50 = 1.0 nM 9.0 Inhibition of mTOR (unknown origin) 29211480
Serine/threonine-protein kinase mTOR IC50 = 1.6 nM 8.8 Inhibition of mTOR 20166697
Serine/threonine-protein kinase mTOR IC50 = 1.6 nM 8.8 Inhibition of mTOR (unknown origin) -
Serine/threonine-protein kinase mTOR IC50 = 1.6 nM 8.8 Inhibition of mTOR (unknown origin) 34894440
Serine/threonine-protein kinase mTOR IC50 = 2.1 nM 8.68 Inhibition of mTOR (unknown origin) using U-Light-4E-BP1 peptide as a substrate ... 34971874
Serine/threonine-protein kinase mTOR IC50 = 2.1 nM 8.68 Inhibition of mTOR (unknown origin) by Lance ultra assay 38661655
Serine/threonine-protein kinase mTOR IC50 = 2.5 nM 8.6 Inhibition of mTOR (unknown origin) measured after 45 mins by LANCE Ultra assay 33440319

Literature References

PubMed DOI Target Context # Activities
38661655 10.1021/acs.jmedchem.4c00173 ADMET 41
38661655 10.1021/acs.jmedchem.4c00173 MCF7 25
21763134 10.1016/j.bmcl.2011.06.063 Mus musculus 10
34971874 10.1016/j.ejmech.2021.114055 ADMET 9
20166697 10.1021/jm901830p Mus musculus 8
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
29191878 10.1126/science.aan4368 Unchecked 4
20166697 10.1021/jm901830p Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 3
20166697 10.1021/jm901830p Serine/threonine-protein kinase mTOR 3
20166697 10.1021/jm901830p MDA-MB-361 3
34971874 10.1016/j.ejmech.2021.114055 HCT-116 3
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
21763134 10.1016/j.bmcl.2011.06.063 Liver microsomes 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
20166697 10.1021/jm901830p RAC-alpha serine/threonine-protein kinase 2
20166697 10.1021/jm901830p Unchecked 2
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 2
38661655 10.1021/acs.jmedchem.4c00173 RAC-alpha serine/threonine-protein kinase 1
20166697 10.1021/jm901830p Nitric oxide synthase 3 1
20166697 10.1021/jm901830p No relevant target 1

Data from ChEMBL 36 via Core Engine