acalabrutinib 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: 1.58
  • 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:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Oct. 31, 2017 FDA ACERTA PHARMA BV

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 51.64 39.37 24 137 335524 46350377

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 113.76 38.38 64 323 357219 29594872

Pharmacologic Action:

SourceCodeDescription
ATC L01EL02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Bruton's tyrosine kinase (BTK) inhibitors
FDA MoA N0000020001 Tyrosine Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:68495 type i programmed cell-death inducer
CHEBI has role CHEBI:76617 abl inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Mantle cell lymphoma indication 443487006

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)

None

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, 2022 NEW CHEMICAL ENTITY
100MG CALQUENCE ASTRAZENECA N210259 Oct. 31, 2017 RX CAPSULE ORAL Nov. 21, 2022 TREATMENT OF ADULT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)
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
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
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR IC50 7.80 SCIENTIFIC LITERATURE
Tyrosine-protein kinase Lyn Kinase INHIBITOR EC50 6 IUPHAR

External reference:

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

Pharmaceutical products:

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