acalabrutinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5260 1420477-60-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • acalabrutinib
  • ACP-196
  • calquence
Acalabrutinib is a small-molecule inhibitor of BTK. Acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B cell antigen receptor (BCR) and cytokine receptor pathways. In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, an adhesion. In nonclinical studies, acalabrutinib inhibited BTK mediated activation of downstream signaling proteins CD86 and CD69 and inhibited malignant B-cell proliferation and survival.
  • Molecular weight: 465.52
  • Formula: C26H23N7O2
  • CLOGP: 2.05
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 2
  • TPSA: 118.51
  • ALOGS: -4.63
  • ROTB: 5
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O

ADMET properties:

PropertyValueReference
S (Water solubility) 0.05 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Approvals:

DateAgencyCompanyOrphan
Nov. 5, 2020 EMA AstraZeneca AB
Oct. 31, 2017 FDA ACERTA PHARMA BV
Jan. 22, 2021 PMDA ASTRAZENECA K.K.

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
Death 169.45 36.37 89 830 374292 63113811
Malignant neoplasm progression 40.71 36.37 21 898 82100 63406003

FDA Adverse Event Reporting System (Male)

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
Death 514.04 28.39 275 1312 397774 34557570
COVID-19 63.62 28.39 41 1546 77509 34877835
Malignant neoplasm progression 56.54 28.39 40 1547 88006 34867338
Tumour lysis syndrome 36.37 28.39 17 1570 17042 34938302
Babesiosis 34.67 28.39 6 1581 145 34955199

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
Death 402.16 27.68 211 1611 566303 79176263
COVID-19 57.84 27.68 39 1783 157635 79584931
Malignant neoplasm progression 45.96 27.68 32 1790 135958 79606608
Tumour lysis syndrome 35.28 27.68 15 1807 23924 79718642
Babesiosis 33.52 27.68 6 1816 357 79742209
Gastroenteritis bacterial 32.25 27.68 6 1816 443 79742123
Atrial fibrillation 29.58 27.68 29 1793 197857 79544709

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EL02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Bruton's tyrosine kinase (BTK) inhibitors
MeSH PA D000970 Antineoplastic Agents
FDA MoA N0000020001 Tyrosine Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:68495 Type I cell-death inducers
CHEBI has role CHEBI:76617 BTK inhibitor

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

DiseaseRelationSNOMED_IDDOID
Chronic lymphocyticleukemia/small lymphocytic lymphoma indication 92814006
Mantle cell lymphoma indication 443487006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.34 acidic
pKa2 3.25 Basic
pKa3 2.49 Basic
pKa4 1.5 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10239883 July 11, 2032 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10239883 July 11, 2032 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9758524 July 11, 2032 TREATMENT OF ADULT PATIENTS WITH MANTLE CELL LYMPHOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10272083 Jan. 21, 2035 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA BY ADMINISTERING 100MG OF ACALABRUTINIB TWICE DAILY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10272083 Jan. 21, 2035 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LEUKEMIA BY ADMINISTERING 100 MG OF ACALABRUTINIB TWICE DAILY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10272083 Jan. 21, 2035 TREATMENT OF ADULT PATIENTS WITH MANTLE CELL LYMPHOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY BY ADMINISTERING 100 MG OF ACALABRUTINIB TWICE DAILY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10272083 Jan. 21, 2035 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA BY ADMINISTERING 100 MG OF ACALABRUTINIB TWICE DAILY IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10272083 Jan. 21, 2035 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB BY ADMINISTERING 100 MG OF ACALABRUTINIB TWICE DAILY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10272083 Jan. 21, 2035 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED SMALL LYMPHOCYTIC LEUKEMIA BY ADMINISTERING 100 MG OF ACALABRUTINIB TWICE DAILY IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10272083 Jan. 21, 2035 TREATMENT OF ADULT PATIENTS WITH SMALL LYMPHOCYTIC LEUKEMIA BY ADMINISTERING 100MG OF ACALABRUTINIB TWICE DAILY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10167291 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10167291 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LEUKEMIA
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10167291 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH MANTLE CELL LYMPHOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10167291 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10167291 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10167291 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED SMALL LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 10167291 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH SMALL LYMPHOCYTIC LEUKEMIA
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9796721 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9796721 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LEUKEMIA
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9796721 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH MANTLE CELL LYMPHOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9796721 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9796721 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9796721 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH PREVIOUSLY UNTREATED SMALL LYMPHOCYTIC LEUKEMIA IN COMBINATION WITH OBINUTUZUMAB
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL 9796721 July 1, 2036 TREATMENT OF ADULT PATIENTS WITH SMALL LYMPHOCYTIC LEUKEMIA

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL Oct. 31, 2024 TREATMENT OF ADULT PATIENTS WITH MANTLE CELL LYMPHOMA (MCL) WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL Nov. 21, 2026 INDICATED FOR THE TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tyrosine-protein kinase BTK Kinase INHIBITOR IC50 8.29 SCIENTIFIC LITERATURE DRUG LABEL
Epidermal growth factor receptor Kinase IC50 5.45 CHEMBL
Receptor tyrosine-protein kinase erbB-2 Kinase Kd 8.13 CHEMBL
Tyrosine-protein kinase Lyn Kinase INHIBITOR EC50 6 IUPHAR
Tyrosine-protein kinase ITK/TSK Kinase Kd 4.92 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 7.75 CHEMBL
Tyrosine-protein kinase JAK3 Kinase Kd 5.52 CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR IC50 7.80 SCIENTIFIC LITERATURE
Cytoplasmic tyrosine-protein kinase BMX Kinase INHIBITOR IC50 7.34 SCIENTIFIC LITERATURE
Tyrosine-protein kinase Tec Kinase INHIBITOR IC50 7.03 SCIENTIFIC LITERATURE
Tyrosine-protein kinase TXK Kinase INHIBITOR IC50 6.43 SCIENTIFIC LITERATURE
Platelet glycoprotein VI Unclassified IC50 5.92 CHEMBL

External reference:

IDSource
I42748ELQW UNII
4037065 VANDF
C4078312 UMLSCUI
CHEBI:167707 CHEBI
CHEMBL3707348 ChEMBL_ID
71226662 PUBCHEM_CID
DB11703 DRUGBANK_ID
CHEMBL4594293 ChEMBL_ID
D10893 KEGG_DRUG
10150 INN_ID
8912 IUPHAR_LIGAND_ID
263870 MMSL
33203 MMSL
d08672 MMSL
017393 NDDF
763037006 SNOMEDCT_US
763502000 SNOMEDCT_US
1986808 RXNORM
C000604908 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
CALQUENCE HUMAN PRESCRIPTION DRUG LABEL 1 0310-0512 CAPSULE, GELATIN COATED 100 mg ORAL NDA 27 sections
CALQUENCE HUMAN PRESCRIPTION DRUG LABEL 1 0310-0512 CAPSULE, GELATIN COATED 100 mg ORAL NDA 27 sections
CALQUENCE HUMAN PRESCRIPTION DRUG LABEL 1 0310-0512 CAPSULE, GELATIN COATED 100 mg ORAL NDA 27 sections
CALQUENCE HUMAN PRESCRIPTION DRUG LABEL 1 0310-0512 CAPSULE, GELATIN COATED 100 mg ORAL NDA 27 sections
CALQUENCE HUMAN PRESCRIPTION DRUG LABEL 1 0310-3512 TABLET, FILM COATED 100 mg ORAL NDA 26 sections