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Compound Detail

CHEMBL2325741

CAPIVASERTIB
💊 Approved Drug
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💊 Approved Drug
NC1(C(=O)N[C@@H](CCO)c2ccc(Cl)cc2)CCN(c2nc[nH]c3nccc2-3)CC1

Basic Information

ChEMBL ID CHEMBL2325741
Name CAPIVASERTIB
Phase Approved
Structure Type MOL
InChI Key JDUBGYFRJFOXQC-KRWDZBQOSA-N
Therapeutic ✓ Yes

Known Names

AZC5363 Azd 5363 Azd-5363 AZD5363 Capivasertib Truqap
58
Targets
103
Activities
3
Assay Types
17
PK Parameters
20
Publications
6
Known Names
19
Indications
1
Mechanisms

Molecular Properties

428.9
MW (Da)
2.10
ALogP
6
HBA
4
HBD
120.2
PSA (Ų)
0.48
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2023
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product First in Class
USAN Stem -sertib
USAN Year 2017

Extended Properties

Molecular Formula C21H25ClN6O2
MW 428.92
Aromatic Rings 1
Heavy Atoms 30
NP-Likeness -0.43

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, Castration-Resistant Adenocarcinoma Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Lymphoma, Follicular Meningioma Multiple Myeloma Prostatic Neoplasms Stomach Neoplasms Stomach Neoplasms Triple Negative Breast Neoplasms Hematologic Neoplasms Hereditary Breast and Ovarian Cancer Syndrome Uterine Cervical Neoplasms Uterine Neoplasms

ATC Classification

L01EX27
capivasertib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 66 meas. best 9.05
Kd 28 meas. best 6.62
EC50 9 meas. best 6.72

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
RAC-alpha serine/threonine-protein kinase
CHEMBL4282
IC50 9.05 8.3642 0.9 12
Serine/threonine-protein kinase AKT
CHEMBL2111353
IC50 8.52 8.52 3.0 1
RAC-beta serine/threonine-protein kinase
CHEMBL2431
IC50 8.3 8.15 5.0 6
Unchecked
CHEMBL612545
IC50 8.22 6.6277 6.0 13
RAC-gamma serine/threonine-protein kinase
CHEMBL4816
IC50 8.15 8.12 7.0 5
Rho-associated protein kinase 2
CHEMBL2973
IC50 7.25 7.25 56.0 1
LNCaP
CHEMBL612518
IC50 6.75 6.545 178.0 2
ZR-75-1
CHEMBL614393
EC50 6.72 6.72 191.0 2
cAMP-dependent protein kinase catalytic subunit beta
CHEMBL2918
Kd 6.62 6.62 239.0 1
cGMP-dependent protein kinase 1
CHEMBL4273
Kd 6.53 6.53 297.0 1
Rho-associated protein kinase 2
CHEMBL2973
Kd 6.49 6.49 324.0 1
LIM domain kinase 1
CHEMBL3836
Kd 6.45 6.45 357.0 1
cAMP-dependent protein kinase catalytic subunit alpha
CHEMBL4101
Kd 6.41 6.41 387.0 1
Rho-associated protein kinase 1
CHEMBL3231
IC50 6.33 6.33 470.0 1
Dual specificity protein kinase CLK1
CHEMBL4224
Kd 6.32 6.32 475.0 1
T47D
CHEMBL614361
EC50 6.32 6.32 475.0 2
LIM domain kinase 2
CHEMBL5932
Kd 6.32 6.32 477.0 1
Dual specificity protein kinase CLK4
CHEMBL4203
Kd 6.29 6.29 513.0 1
MCF7
CHEMBL387
EC50 6.26 6.26 555.0 1
Rho-associated protein kinase 1
CHEMBL3231
Kd 6.15 6.15 706.0 1
Unchecked
CHEMBL612545
Kd 6.06 6.06 879.0 1
AN3-CA
CHEMBL1075392
EC50 6.06 6.06 869.0 2
Fibroblast growth factor receptor 1
CHEMBL3650
Kd 6.06 6.06 865.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
Kd 5.96 5.96 1107.0 1
Serine/threonine-protein kinase N1
CHEMBL3384
Kd 5.8 5.8 1577.0 1
BT-474
CHEMBL614529
EC50 5.79 5.79 1605.0 1
Protein kinase C alpha type
CHEMBL299
Kd 5.76 5.76 1733.0 1
5'-AMP-activated protein kinase catalytic subunit alpha-1
CHEMBL4045
Kd 5.74 5.74 1821.0 1
Mitogen-activated protein kinase kinase kinase kinase 3
CHEMBL5432
Kd 5.72 5.72 1900.0 1
Mitogen-activated protein kinase kinase kinase 11
CHEMBL2708
Kd 5.7 5.7 1999.0 1
Serine/threonine-protein kinase D3
CHEMBL2595
Kd 5.66 5.66 2207.0 1
Serine/threonine-protein kinase D2
CHEMBL4900
Kd 5.65 5.65 2246.0 1
SARS-CoV-2
CHEMBL4303835
IC50 5.63 5.63 2330.0 1
Protein kinase C beta type
CHEMBL3045
Kd 5.61 5.61 2431.0 1
5'-AMP-activated protein kinase subunit gamma-1
CHEMBL2393
Kd 5.61 5.61 2445.0 1
RAC-beta serine/threonine-protein kinase
CHEMBL2431
Kd 5.6 5.6 2490.0 1
5'-AMP-activated protein kinase subunit gamma-2
CHEMBL2453
Kd 5.57 5.57 2711.0 1
NCI-H1975
CHEMBL614348
IC50 5.57 5.325 2700.0 2
Protein kinase C delta type
CHEMBL2996
Kd 5.55 5.55 2809.0 1
RAC-alpha serine/threonine-protein kinase
CHEMBL4282
Kd 5.41 5.41 3883.0 1
HaCaT
CHEMBL614392
IC50 5.38 5.38 4200.0 1
MCF7
CHEMBL387
IC50 5.38 5.38 4200.0 1
Protein kinase C theta type
CHEMBL3920
Kd 5.37 5.37 4246.0 1
OVCAR-8
CHEMBL612555
IC50 5.35 5.245 4480.0 2
Beta-adrenergic receptor kinase 1
CHEMBL4079
Kd 5.31 5.31 4859.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 5.28 5.21 5200.0 2
HCT-116
CHEMBL394
IC50 5.28 5.28 5200.0 1
SK-OV-3
CHEMBL614925
IC50 5.2 5.2 6320.0 1
HepG2
CHEMBL395
IC50 5.17 5.17 6700.0 1
AGS
CHEMBL613860
IC50 5.02 5.02 9600.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 22.0 mL.min-1.kg-1 Canis lupus familiaris
CL 95.0 mL.min-1.kg-1 Rattus norvegicus
CL 207.0 mL.min-1.kg-1 Mus musculus
CL 14.0 mL.min-1.g-1 Homo sapiens
CL 16.0 mL.min-1.g-1 Mus musculus
F 37.0 % Canis lupus familiaris
F 13.0 % Rattus norvegicus
F 86.0 % Mus musculus
Fu 0.192 - Canis lupus familiaris
Fu 0.235 - Rattus norvegicus
Fu 0.143 - Mus musculus
Fu 0.223 - Homo sapiens
T1/2 1.7 hr Canis lupus familiaris
T1/2 0.5 hr Rattus norvegicus
T1/2 0.2 hr Mus musculus
T1/2 0.55 hr Homo sapiens
T1/2 1.45 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 IC50 = 0.9 nM 9.05 Covalent-allosteric inhibition of full length N-terminal his6-tagged AKT (2 to 4... 30996949
RAC-alpha serine/threonine-protein kinase IC50 = 1.0 nM 9.0 Inhibition of N-terminal His6-tagged TEV protease fused wild-type AKT1 (2 to 446... 31584233
RAC-alpha serine/threonine-protein kinase IC50 = 3.0 nM 8.52 Inhibition of AKT1 (unknown origin) 38183778
Serine/threonine-protein kinase AKT IC50 = 3.0 nM 8.52 Inhibition of AKT phosphorylation in human MDA-MB-231 incubated for 18 hrs by We... 38592948
RAC-alpha serine/threonine-protein kinase IC50 = 3.0 nM 8.52 Inhibition of recombinant Akt1 (unknown origin) using 5-FAM-labeled peptide as s... 23394218
RAC-alpha serine/threonine-protein kinase IC50 = 3.0 nM 8.52 Inhibition of Akt-1 (unknown origin) 32599323
RAC-alpha serine/threonine-protein kinase IC50 = 3.0 nM 8.52 Inhibition of AKT1 (unknown origin) 38295689
RAC-alpha serine/threonine-protein kinase IC50 = 3.2 nM 8.49 In Vitro AKT1 Kinase Assay: Following addition of compound or control to the ass... -
RAC-alpha serine/threonine-protein kinase IC50 = 3.2 nM 8.49 In Vitro Kinase Assay: For Echo dosing the solvent was 100% DMSO. A master plate... -
RAC-beta serine/threonine-protein kinase IC50 = 5.0 nM 8.3 Inhibition of N-terminal His6-tagged TEV protease fused wild-type AKT2 (2 to 447... 31584233
Unchecked IC50 = 6.0 nM 8.22 Inhibition of P70S6K (unknown origin) after 30 mins by 33P-ATP filter-binding as... 23394218
RAC-gamma serine/threonine-protein kinase IC50 = 7.0 nM 8.15 Inhibition of Akt-3 (unknown origin) 32599323
RAC-beta serine/threonine-protein kinase IC50 = 7.0 nM 8.15 Inhibition of Akt-2 (unknown origin) 32599323
Unchecked IC50 = 7.0 nM 8.15 Inhibition of PKA (unknown origin) using 5-FAM-labeled peptide as substrate afte... 23394218
RAC-gamma serine/threonine-protein kinase IC50 = 7.0 nM 8.15 Inhibition of AKT3 (unknown origin) 38183778
RAC-beta serine/threonine-protein kinase IC50 = 7.0 nM 8.15 Inhibition of AKT2 (unknown origin) 38183778
RAC-beta serine/threonine-protein kinase IC50 = 8.0 nM 8.1 Inhibition of AKT2 (unknown origin) 38592948
RAC-alpha serine/threonine-protein kinase IC50 = 8.0 nM 8.1 Inhibition of AKT1 (unknown origin) 38592948
RAC-gamma serine/threonine-protein kinase IC50 = 8.0 nM 8.1 Inhibition of AKT3 (unknown origin) 38295689
RAC-beta serine/threonine-protein kinase IC50 = 8.0 nM 8.1 Inhibition of recombinant Akt2 (unknown origin) using 5-FAM-labeled peptide as s... 23394218

Literature References

PubMed DOI Target Context # Activities
34375113 10.1021/acs.jmedchem.1c00815 HaCaT 18
23394218 10.1021/jm301762v Unchecked 16
23394218 10.1021/jm301762v Mus musculus 9
23394218 10.1021/jm301762v Plasma 4
23394218 10.1021/jm301762v Rattus norvegicus 4
23394218 10.1021/jm301762v Canis familiaris 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
30996949 10.1039/c8sc05212c ADMET 4
29191878 10.1126/science.aan4368 Unchecked 4
23394218 10.1021/jm301762v NON-PROTEIN TARGET 3
23394218 10.1021/jm301762v Hepatocyte 3
35119851 10.1021/acs.jmedchem.1c02165 Unchecked 3
34917257 10.1021/acsmedchemlett.1c00504 RAC-alpha serine/threonine-protein kinase 3
23394218 10.1021/jm301762v Rho-associated protein kinase 2 2
23394218 10.1021/jm301762v RAC-gamma serine/threonine-protein kinase 2
23394218 10.1021/jm301762v RAC-beta serine/threonine-protein kinase 2
23394218 10.1021/jm301762v RAC-alpha serine/threonine-protein kinase 2
27089211 10.1016/j.ejmech.2016.03.074 NON-PROTEIN TARGET 2
34375113 10.1021/acs.jmedchem.1c00815 786-0 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2

Data from ChEMBL 36 via Core Engine