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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H23N7O2
Molecular Weight 465.5065
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ACALABRUTINIB

SMILES

CC#CC(=O)N1CCC[C@H]1C2=NC(=C3N2C=CN=C3N)C4=CC=C(C=C4)C(=O)NC5=NC=CC=C5

InChI

InChIKey=WDENQIQQYWYTPO-IBGZPJMESA-N
InChI=1S/C26H23N7O2/c1-2-6-21(34)32-15-5-7-19(32)25-31-22(23-24(27)29-14-16-33(23)25)17-9-11-18(12-10-17)26(35)30-20-8-3-4-13-28-20/h3-4,8-14,16,19H,5,7,15H2,1H3,(H2,27,29)(H,28,30,35)/t19-/m0/s1

HIDE SMILES / InChI

Molecular Formula C26H23N7O2
Molecular Weight 465.5065
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Acalabrutinib, also known as ACP-196, is a novel irreversible second-generation Bruton’s tyrosine kinase (BTK) inhibitor, which prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and that, was rationally designed to be more potent and selective than ibrutinib. This drug in clinical trials phase III for treatment the treatment of relapsed chronic lymphocytic leukemia. Also in combination with others drugs, Acalabrutinib in phase II of clinical trials for the treatment Glioblastoma Multiforme, Mantle Cell Lymphoma, Squamous Cell Carcinoma of the Head and Neck, Rheumatoid Arthritis and some others.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.
2016 Jan 28

Sample Use Guides

In Vivo Use Guide
for Chronic Lymphocytic Leukemia: 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion.
Route of Administration: Oral
In Vitro Use Guide
The differential effects of acalabrutinib on primary chronic lymphocytic leukemia (CLL) cells, T cells, NK cells, and epithelial cells were studied by signaling and functional assays. Acalabrutinib inhibited purified ruton’s tyrosine kinase (BTK) with an IC50 of 3 nM and EC50 of 8 nM in a human whole-blood CD69 B cell activation assay. Acalabrutinib was shown to have improved target specificity over ibrutinib with 323-, 94-, 19-, and 9-fold selectivity over the other TEC kinase family members (ITK, TXK, BMX, and TEC, respectively) and no activity against EGFR.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:55:42 UTC 2019
Edited
by admin
on Mon Oct 21 20:55:42 UTC 2019
Record UNII
I42748ELQW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ACALABRUTINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
ACALABRUTINIB [WHO-DD]
Common Name English
ACALABRUTINIB [JAN]
Common Name English
ACP-196
Code English
BENZAMIDE, 4-(8-AMINO-3-((2S)-1-(1-OXO-2-BUTYN-1-YL)-2-PYRROLIDINYL)IMIDAZO(1,5-A)PYRAZIN-1-YL)-N-2-PYRIDINYL-
Systematic Name English
ACALABRUTINIB [INN]
Common Name English
CALQUENCE
Brand Name English
ACALABRUTINIB [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C124801
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
EU-Orphan Drug EU/3/16/1625
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
FDA ORPHAN DRUG 489015
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
FDA ORPHAN DRUG 477415
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
FDA ORPHAN DRUG 488915
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
Code System Code Type Description
NCI_THESAURUS
C113442
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
PRIMARY
CAS
1639823-20-3
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
NO STRUCTURE GIVEN
CAS
1420477-60-6
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
PRIMARY
EVMPD
SUB182073
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
PRIMARY
PUBCHEM
71226662
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
PRIMARY
ChEMBL
CHEMBL3707348
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
PRIMARY
INN
10150
Created by admin on Mon Oct 21 20:55:42 UTC 2019 , Edited by admin on Mon Oct 21 20:55:42 UTC 2019
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
In the mass balance study, 84% of the dose was received in the feces and 12% of the dose was recovered in the urine, with less than 1% of the dose excreted as unchanged acalabrutinib in urine.
AMOUNT EXCRETED
URINE
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
Acalabrutinib forms a covalent bond with Cys481 in the BTK adenosine triphosphate (ATP).
IRREVERSIBLE INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
OFF TARGET->NON-INHIBITOR
at 10 micromolar 25% inhibition
IC50
TRANSPORTER -> SUBSTRATE
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION