capivasertib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
serine/threonine kinase inhibitors 5752 1143532-39-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • capivasertib
  • AZD5363
  • AZ1295230
  • truqap
Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3) and inhibits phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA). In vitro, capivasertib reduced growth of breast cancer cell lines including those with relevant PIK3CA or AKT1 mutations or PTEN alteration. In vivo, capivasertib alone and in combination with fulvestrant inhibited tumor growth of mouse xenograft models including estrogen receptor positive breast cancer models with alterations in PIK3CA, AKT1, and PTEN.
  • Molecular weight: 428.92
  • Formula: C21H25ClN6O2
  • CLOGP: 2.10
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 4
  • TPSA: 120.16
  • ALOGS:
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.46 g O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.137 Moderate 0.66
caco2-efflux Caco-2 efflux ratio (BA/AB) 26.485 Moderate 0.66
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 2.618 10^-6 cm/s Moderate 0.66
dh-clint Dog hepatocyte intrinsic clearance 5.117 uL/min/10^6 cells Moderate 0.66
dppb Dog plasma protein binding (% unbound) 26.320 % Moderate 0.66
fcs-ppb Fetal calf serum protein binding (% unbound) 46.900 % Moderate 0.66
herg hERG pIC50 4.424 pIC50 Moderate 0.66
hh-clint Human hepatocyte intrinsic clearance 3.963 uL/min/10^6 cells Moderate 0.66
hlm-clint Human liver microsomal intrinsic clearance 30.339 uL/min/mg protein Moderate 0.66
hppb Human plasma protein binding (% unbound) 28.470 % Moderate 0.66
kinase-safety-class AAK1,ACVR2A,ACVR2B,ACVRL1,AKT1,AKT2,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BRAF,CAMK2B,CAMK2D,CDK9,CHEK1,CLK2,CLK4,CSF1R,DDR1,DYRK1B,EGFR,ERBB2,FGFR1,FLT3,GAK,GRK1,GRK2,GRK3,GSK3B,ITK,JAK1,JAK2,KDR,KIT,LCK,MAP2K1,MAP2K6,MAP3K10,MAP3K11,MAP3K21,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK3,MAPK7,MARK4,MELK,MET,NTRK1,NUAK1,PAK4,PAK5,PDK1,PDK2,PDK4,PIK3CD,PRKAA1,PRKAA2,PRKACA,PRKCD,PRKDC,PRKG1,RET,ROCK1,ROCK2,RPS6KA1,SGK1,SIK2,SIK3,STK33,SYK,TTK,ULK1,ULK2 79
kinase-selectivity-class AKT1,AKT2,AKT3,CHEK1,CLK2,CSF1R,FGFR1,GRK2,GRK3,JAK1,JAK2,JAK3,LCK,MAP2K1,MAP3K10,MAP4K3,MAPK1,MARK3,MARK4,NTRK3,NUAK1,PAK4,PDK1,PDK4,PRKACA,PRKCD,PRKG1,RET,ROCK1,ROCK2,STK33,SYK 32
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 11.995 Moderate 0.66
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 8.570 Moderate 0.66
mh-clint Mouse hepatocyte intrinsic clearance 25.468 Moderate 0.66
mppb Mouse plasma protein binding (% unbound) 23.980 Moderate 0.66
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 10.568 Moderate 0.66
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 42.630 % Moderate 0.66
rat-kpuu-brain Rat brain Kpuu 0.007 % Moderate 0.66
rh-clint Rat hepatocyte intrinsic clearance 20.230 uL/min/10^6 cells Moderate 0.66
rh-fuinc Rat hepatocyte fraction unbound in incubation 73.050 % Moderate 0.66
rppb Rat plasma protein binding (% unbound) 24.580 % Moderate 0.66
solubility-dd Solubility at pH 7.4 in DMSO 353.183 uM Moderate 0.66

Approvals:

DateAgencyCompanyOrphan
Nov. 16, 2023 FDA ASTRAZENECA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperglycaemia 875.98 52.63 215 2299 50755 90575178
Rash 349.72 52.63 234 2280 795866 89830067
Diabetic ketoacidosis 233.19 52.63 65 2449 24342 90601591
Death 232.24 52.63 148 2366 456403 90169530
Erythema multiforme 210.48 52.63 52 2462 12194 90613739
Diarrhoea 192.86 52.63 177 2337 939013 89686920
Malignant neoplasm progression 174.58 52.63 76 2438 106794 90519139
Disease progression 167.44 52.63 83 2431 156532 90469401
Hyperglycaemic hyperosmolar nonketotic syndrome 105.45 52.63 20 2494 1349 90624584
Metastases to liver 98.32 52.63 35 2479 28772 90597161
Blood glucose increased 60.90 52.63 36 2478 95210 90530723

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperglycaemia 473.43 47.40 128 1465 84962 110502744
Erythema multiforme 196.01 47.40 48 1545 21049 110566657
Rash 164.20 47.40 116 1477 820848 109766858
Diabetic ketoacidosis 150.08 47.40 45 1548 42013 110545693
Diarrhoea 110.73 47.40 106 1487 1139399 109448307
Hyperglycaemic hyperosmolar nonketotic syndrome 102.86 47.40 20 1573 2989 110584717
Metastases to liver 88.96 47.40 29 1564 35357 110552349
Malignant neoplasm progression 82.12 47.40 43 1550 174524 110413182
Metastases to bone 48.87 47.40 18 1575 31354 110556352

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EX27 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Other protein kinase inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D019380 Anti-HIV Agents
MeSH PA D044966 Anti-Retroviral Agents
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50925 EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor

Related Drugs by ATC class:

L01EX Other protein kinase inhibitors 21 drugs
avapritinibcabozantinibentrectinibgilteritiniblarotrectiniblenvatinibmidostaurinnintedanibpazopanibpexidartinibpralsetinibquizartinib show all 21 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Hormone receptor pozitive breast cancer indication 417181009
Human epidermal growth factor 2 negative carcinoma of breast indication 431396003




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 10654855 Oct. 10, 2028 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 11236095 Oct. 10, 2028 TREATMENT IN COMBINATION WITH ABIRATERONE AND PREDNISONE OF METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR -SENSITIVE (MAPMN/S) PROSTATE CANCER THAT IS PTEN-DEFICIENT
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 11760760 Oct. 10, 2028 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 12252495 Oct. 10, 2028 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 9492453 Oct. 10, 2028 TREATMENT IN COMBINATION WITH ABIRATERONE AND PREDNISONE OF METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR -SENSITIVE (MAPMN/S) PROSTATE CANCER THAT IS PTEN-DEFICIENT
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 10654855 Oct. 10, 2028 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 11236095 Oct. 10, 2028 TREATMENT IN COMBINATION WITH ABIRATERONE AND PREDNISONE OF METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR -SENSITIVE (MAPMN/S) PROSTATE CANCER THAT IS PTEN-DEFICIENT
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 11760760 Oct. 10, 2028 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 12252495 Oct. 10, 2028 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 9492453 Oct. 10, 2028 TREATMENT IN COMBINATION WITH ABIRATERONE AND PREDNISONE OF METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR -SENSITIVE (MAPMN/S) PROSTATE CANCER THAT IS PTEN-DEFICIENT
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 8101623 March 10, 2030 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 8101623 March 10, 2030 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 10039766 April 16, 2033 TREATMENT IN COMBINATION WITH ABIRATERONE AND PREDNISONE OF METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR -SENSITIVE (MAPMN/S) PROSTATE CANCER THAT IS PTEN-DEFICIENT
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 10039766 April 16, 2033 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 10039766 April 16, 2033 TREATMENT IN COMBINATION WITH ABIRATERONE AND PREDNISONE OF METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR -SENSITIVE (MAPMN/S) PROSTATE CANCER THAT IS PTEN-DEFICIENT
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL 10039766 April 16, 2033 TREATMENT WITH FULVESTRANT OF HR-POS. HER2-NEG. LOCALLY ADVANCED OR METASTATIC BREAST CANCER WITH PIK3CA/AKT1/PTEN-ALTERATION(S) FOLLOWING PROGRESSION ON ENDOCRINE THERAPY IN THE METASTATIC SETTING OR RECURRENCE ON OR WITHIN 12 MONTHS OF ADJUVANT THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL Nov. 16, 2028 NEW CHEMICAL ENTITY
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL Nov. 16, 2028 NEW CHEMICAL ENTITY
160MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL June 12, 2029 IN COMBINATION WITH ABIRATERONE AND PREDNISONE FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR-SENSITIVE PROSTATE CANCER THAT IS PTEN-DEFICIENT AS DETECTED BY AN FDA-AUTHORIZED TEST
200MG TRUQAP ASTRAZENECA N218197 Nov. 16, 2023 RX TABLET ORAL June 12, 2029 IN COMBINATION WITH ABIRATERONE AND PREDNISONE FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC ANDROGEN PATHWAY MODULATION-NAIVE OR-SENSITIVE PROSTATE CANCER THAT IS PTEN-DEFICIENT AS DETECTED BY AN FDA-AUTHORIZED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
RAC-alpha serine/threonine-protein kinase Kinase INHIBITOR IC50 8.49 DRUG LABEL DRUG LABEL
RAC-beta serine/threonine-protein kinase Kinase INHIBITOR IC50 8.07 DRUG LABEL DRUG LABEL
RAC-gamma serine/threonine-protein kinase Kinase INHIBITOR IC50 8.10 IUPHAR DRUG LABEL
Protein kinase C delta type Kinase Kd 5.55 CHEMBL
cAMP-dependent protein kinase catalytic subunit beta Kinase Kd 6.62 CHEMBL
Rho-associated protein kinase 2 Kinase IC50 7.25 CHEMBL
Protein kinase C alpha type Kinase Kd 5.76 CHEMBL
LIM domain kinase 1 Kinase Kd 6.45 CHEMBL
5'-AMP-activated protein kinase catalytic subunit alpha-1 Kinase Kd 5.74 CHEMBL
Fibroblast growth factor receptor 1 Kinase Kd 6.06 CHEMBL
Serine/threonine-protein kinase N1 Kinase Kd 5.80 CHEMBL
Protein kinase C theta type Kinase Kd 5.37 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 6.32 CHEMBL
Dual specificity protein kinase CLK4 Kinase Kd 6.29 CHEMBL
Beta-adrenergic receptor kinase 1 Kinase Kd 5.31 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase Kd 5.96 CHEMBL
Serine/threonine-protein kinase LATS1 Kinase Kd 4.85 CHEMBL
cAMP-dependent protein kinase catalytic subunit alpha Kinase Kd 6.41 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 3 Kinase Kd 5.72 CHEMBL
Mitogen-activated protein kinase kinase kinase 11 Kinase Kd 5.70 CHEMBL
Serine/threonine-protein kinase D2 Kinase Kd 5.65 CHEMBL
Serine/threonine-protein kinase D3 Kinase Kd 5.66 CHEMBL
cGMP-dependent protein kinase 1 Kinase Kd 6.53 CHEMBL
5'-AMP-activated protein kinase subunit gamma-1 Kinase Kd 5.61 CHEMBL
5'-AMP-activated protein kinase subunit gamma-2 Kinase Kd 5.57 CHEMBL
Glycogen synthase kinase-3 beta Kinase INHIBITOR IC50 6.38 DRUG LABEL
Serine/threonine-protein kinase MRCK gamma Kinase INHIBITOR IC50 8.11 DRUG LABEL
Proline-rich AKT1 substrate 1 Kinase INHIBITOR IC50 6.01 DRUG LABEL
LIM domain kinase 2 Kinase Kd 6.32 CHEMBL
Rho-associated protein kinase 1 Kinase IC50 6.33 CHEMBL
Protein kinase C beta type Kinase Kd 5.61 CHEMBL

External reference:

IDSource
0XZ PDB_CHEM_ID
CHEMBL2325741 ChEMBL_ID
C575618 MESH_SUPPLEMENTAL_RECORD_UI
7709 IUPHAR_LIGAND_ID
DB12218 DRUGBANK_ID
43186611000001107 SNOMEDCT_US
4042792 VANDF
C4682387 UMLSCUI
CHEBI:229222 CHEBI
CHEMBL2178577 ChEMBL_ID
10668 INN_ID
25227436 PUBCHEM_CID
374527 MMSL
42192 MMSL
d10136 MMSL
019610 NDDF
WFR23M21IE UNII
2669967 RXNORM
D11371 KEGG_DRUG
C000712547 MESH_SUPPLEMENTAL_RECORD_UI
WFR23M21IE INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TRUQAP HUMAN PRESCRIPTION DRUG LABEL 1 0310-9500 TABLET, FILM COATED 160 mg ORAL NDA 27 sections
TRUQAP HUMAN PRESCRIPTION DRUG LABEL 1 0310-9501 TABLET, FILM COATED 200 mg ORAL NDA 27 sections