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Compound Detail

CHEMBL2177390

IPATASERTIB
🧪 Phase III
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🧪 Phase III
CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)C[C@H]3O)CC1)c1ccc(Cl)cc1

Basic Information

ChEMBL ID CHEMBL2177390
Name IPATASERTIB
Phase Phase III
Structure Type MOL
InChI Key GRZXWCHAXNAUHY-NSISKUIASA-N

Known Names

GDC-0068 Ipatasertib Rg-7440 RG7440
20
Targets
47
Activities
3
Assay Types
5
PK Parameters
20
Publications
4
Known Names
14
Indications
1
Mechanisms

Molecular Properties

458.0
MW (Da)
3.10
ALogP
6
HBA
2
HBD
81.6
PSA (Ų)
0.69
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Natural Product
USAN Stem -sertib
USAN Year 2013

Extended Properties

Molecular Formula C24H32ClN5O2
MW 458.01
Aromatic Rings 2
Heavy Atoms 32
NP-Likeness -0.65

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine/threonine-protein kinase AKT inhibitor INHIBITOR Serine/threonine-protein kinase AKT

Indications

Breast Neoplasms Breast Neoplasms Neoplasms Neoplasms Prostatic Neoplasms Triple Negative Breast Neoplasms Carcinoma, Non-Small-Cell Lung Multiple Myeloma Ovarian Neoplasms Ovarian Neoplasms Prostatic Neoplasms, Castration-Resistant Stomach Neoplasms Stomach Neoplasms Endometrial Neoplasms

Activity Summary

IC50 38 meas. best 8.89
EC50 6 meas. best 6.66
Kd 3 meas. best 9.19

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
RAC-alpha serine/threonine-protein kinase
CHEMBL4282
Kd 9.19 9.19 0.6 1
RAC-alpha serine/threonine-protein kinase
CHEMBL4282
IC50 8.89 8.3075 1.3 8
RAC-gamma serine/threonine-protein kinase
CHEMBL4816
Kd 8.6 8.6 2.5 1
RAC-beta serine/threonine-protein kinase
CHEMBL2431
IC50 8.42 7.748 3.8 5
RAC-gamma serine/threonine-protein kinase
CHEMBL4816
IC50 8.1 7.86 8.0 4
Unchecked
CHEMBL612545
IC50 7.72 6.3325 19.0 4
RAC-beta serine/threonine-protein kinase
CHEMBL2431
Kd 7.46 7.46 35.0 1
cGMP-dependent protein kinase 1
CHEMBL4273
IC50 7.16 7.085 69.0 2
LNCaP
CHEMBL612518
IC50 7.02 7.02 95.0 1
Huh-7
CHEMBL614039
IC50 6.78 6.78 167.0 1
ZR-75-1
CHEMBL614393
EC50 6.66 6.66 219.0 1
CAL-51
CHEMBL1075411
IC50 6.58 6.58 265.2 1
HepG2
CHEMBL395
IC50 6.57 6.57 268.0 1
RL95-2
CHEMBL2366168
IC50 6.48 6.48 331.1 1
T47D
CHEMBL614361
IC50 6.48 6.48 327.8 1
T47D
CHEMBL614361
EC50 6.35 6.35 443.0 1
SMMC-7721
CHEMBL613831
IC50 6.18 6.18 661.0 1
TOV21G
CHEMBL4630716
IC50 6.15 6.15 715.2 1
C-33-A
CHEMBL2366313
IC50 6.14 6.14 726.0 1
AN3-CA
CHEMBL1075392
EC50 6.03 6.03 925.0 1
PC-3
CHEMBL390
IC50 6.0 5.725 1000.0 2
MCF7
CHEMBL387
IC50 6.0 6.0 1000.0 1
BT-474
CHEMBL614529
IC50 6.0 6.0 1000.0 1
ZR-75-1
CHEMBL614393
IC50 5.88 5.88 1316.0 1
BT-474
CHEMBL614529
EC50 5.62 5.62 2371.0 1
MCF7
CHEMBL387
EC50 5.3 5.3 5036.0 1
KU-19-19
CHEMBL1075483
EC50 4.62 4.62 24037.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 3.0 uL.min-1.(10^6cells)-1 Homo sapiens
CL 12.0 mL.min-1.g-1 Homo sapiens
CL 6.0 mL.min-1.g-1 Mus musculus
T1/2 0.65 hr Homo sapiens
T1/2 3.85 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
RAC-alpha serine/threonine-protein kinase Kd = 0.64 nM 9.19 Binding affinity to wild-type human partial length AKT1 expressed in bacterial e... 34855399
RAC-alpha serine/threonine-protein kinase IC50 = 1.3 nM 8.89 Inhibition of N-terminal GST-tagged human AKT1 (104 to 408 residues) expressed i... 34375113
RAC-alpha serine/threonine-protein kinase IC50 = 2.0 nM 8.7 Biochemical Assays: iFLiK and HTRF studies were carried out as described in Z. F... -
RAC-gamma serine/threonine-protein kinase Kd = 2.5 nM 8.6 Binding affinity to wild-type human partial length AKT3 expressed in bacterial e... 34855399
RAC-alpha serine/threonine-protein kinase IC50 = 2.6 nM 8.59 Biochemical Assays: iFLiK and HTRF studies were carried out as described in Z. F... -
RAC-alpha serine/threonine-protein kinase IC50 = 3.5 nM 8.46 Covalent-allosteric inhibition of full length N-terminal his6-tagged AKT (2 to 4... 30996949
RAC-beta serine/threonine-protein kinase IC50 = 3.8 nM 8.42 Inhibition of N-terminal GST-tagged human AKT2 (120 to 481 residues) expressed i... 34375113
RAC-alpha serine/threonine-protein kinase IC50 = 3.8 nM 8.42 Inhibition of recombinant AKT1 (104 to 480 end residues) (unknown origin) cataly... 35679512
RAC-alpha serine/threonine-protein kinase IC50 = 5.0 nM 8.3 Competitive inhibition of wild-type full-length amino-terminal polyhistidine-tag... 22934575
RAC-alpha serine/threonine-protein kinase IC50 = 5.0 nM 8.3 Inhibition of Akt1 (unknown origin) 34411892
RAC-gamma serine/threonine-protein kinase IC50 = 8.0 nM 8.1 Competitive inhibition of wild-type full-length amino-terminal polyhistidine-tag... 22934575
RAC-gamma serine/threonine-protein kinase IC50 = 8.0 nM 8.1 Inhibition of Akt3 (unknown origin) 34411892
RAC-beta serine/threonine-protein kinase IC50 = 18.0 nM 7.75 Competitive inhibition of wild-type full-length amino-terminal polyhistidine-tag... 22934575
RAC-beta serine/threonine-protein kinase IC50 = 18.0 nM 7.75 Inhibition of Akt2 (unknown origin) 34411892
Unchecked IC50 = 19.0 nM 7.72 Inhibition of full length human Akt1 S478G mutant using GRPRTSSFAEGKK as substra... 32007668
RAC-gamma serine/threonine-protein kinase IC50 = 22.0 nM 7.66 Inhibition of recombinant N-terminal GST tagged AKT2 (108 to 479 end residues) (... 35679512
RAC-gamma serine/threonine-protein kinase IC50 = 26.0 nM 7.58 Inhibition of full length human Akt3 S472D mutant using GRPRTSSFAEGKK as substra... 32007668
RAC-beta serine/threonine-protein kinase IC50 = 32.0 nM 7.5 Inhibition of full length human Akt2 S474D mutant using GRPRTSSFAEGKK as substra... 32007668
RAC-beta serine/threonine-protein kinase Kd = 35.0 nM 7.46 Binding affinity to wild-type human partial length AKT2 expressed in bacterial e... 34855399
RAC-beta serine/threonine-protein kinase IC50 = 48.0 nM 7.32 Inhibition of recombinant AKT2 (120 to 481 end residues) (unknown origin) cataly... 35679512

Literature References

PubMed DOI Target Context # Activities
22934575 10.1021/jm301024w MCF7 6
22934575 10.1021/jm301024w Unchecked 6
22934575 10.1021/jm301024w RAC-alpha serine/threonine-protein kinase 6
22934575 10.1021/jm301024w Mus musculus 6
22934575 10.1021/jm301024w PC-3 5
22934575 10.1021/jm301024w cGMP-dependent protein kinase 1 4
30996949 10.1039/c8sc05212c ADMET 4
22934575 10.1021/jm301024w Plasma 4
34855399 10.1021/acs.jmedchem.1c01476 Unchecked 3
22934575 10.1021/jm301024w BT-474 3
32007668 10.1016/j.ejmech.2020.112076 Huh-7 3
35679512 10.1021/acs.jmedchem.2c00527 Unchecked 2
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
22934575 10.1021/jm301024w No relevant target 1
22934575 10.1021/jm301024w RAC-beta serine/threonine-protein kinase 1
22934575 10.1021/jm301024w RAC-gamma serine/threonine-protein kinase 1
- 10.6019/CHEMBL3301361 No relevant target 1
- 10.6019/CHEMBL3301361 ADMET 1

Data from ChEMBL 36 via Core Engine