General
Preferred name
ACALABRUTINIB
Synonyms
ACP-196 ()
Acalabrutinib (ACP-196) ()
AcalabrutinibCS-5356 ()
ACALABRUTINIB MALEATE ()
CALQUENCE ()
Calquence maleate ()
Acalabrutinib maleate anhydrous ()
Acalabrutinib maleate monohydrate ()
P&D ID
PD049821
CAS
1420477-60-6
Tags
available
covalent binder
drug
Approved by
EMA
PMDA
FDA
First approval
2020
2017
Drug indication
Chronic lymphocytic leukaemia
Coronavirus Disease 2019 (COVID-19)
Mantle cell lymphoma
Chronic lymphocytic leukemia
Drug Status
approved
investigational
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Acalabrutinib is an orally available second-generation, irreversible inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK), being investigated for its potential antineoplastic activity (in multiple haematologic malignancies and solid tumours), as well as a potential therapy for rheumatoid arthritis.
PHARMACODYNAMICS
When a dosage of acalabrutinib 100 mg twice daily is administered, a median steady state Bruton Tyrosine Kinase (BTK) occupany of approximately ⥠95% in peripheral blood is maintained over 12 hours allowing for the inactivation of BTK throughout the recommended dosing interval [FDA Label].; ; Additionally, it has been shown that a single dose of acalabrutinib that is four-fold the maximum recommended single dose (ie. 100 mg) does not appear to prolong QTc interval to any clinically significant extent (ie. ⥠10 ms) [FDA Label].
MOA
Mantle Cell Lymphoma (MCL) is a rare yet aggressive type of B-cell non-Hodgkin lymphoma (NHL) with poor prognosis [A31253, L1008]. Subsequently, relapse is common in MCL patients and ultimately represents disease progression [L1008].; ; Lymphoma occurs when immune system lymphocytes grow and multiply uncontrollably. Such cancerous lymphocytes may travel to many parts of the body, including the lymph nodes, spleen, bone marrow, blood, and other organs where they can multiply and form a mass(es) called a tumor. One of the main kinds of lymphocytes that can develop into cancerous lymphomas are the body's own B-lymphocytes (B-cells) [L1008].; ; Bruton Tyrosine Kinase (BTK) is a signalling molecule of the B-cell antigen receptor and cytokine receptor pathways. Such BTK signaling causes the activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion [FDA Label].; ; Acalabrutinib is a small molecule inhibitor of BTK. Both acalabrutinib and its active metabolite, ACP-5862, act to form a covalent bond with a cysteine residue (Cys481) in the BTK active site, leading to inhibition of BTK enzymatic activity [A31253, L1008]. As a result, acalabrutinib inhibits BTK-mediated activation of downstream signaling proteins CD86 and CD69, which ultimately inhibits malignant B-cell proliferation and survival [L1008].; ; Whereas ibrutinib is typically recognized as the first-in-class BTK inhibitor [A31253], acalabrutinib is considered a second generation BTK inhibitor primarily because it demonstrates highter selectivity and inhibition of the targeted activity of BTK while having a much greater IC50 or otherwise virtually no inhibition on the kinase activities of ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1 [A31253]. ; ; In effect, acalabrutinib was rationally designed to be more potent and selective than ibrutinib, all the while demonstrating fewer adverse effects - in theory - because of the drug's minimized bystander effects on targets other than BTK.
HALF-LIFE
After administering a single oral dose of 100 mg acalabrutinib, the median terminal elimination half-life of the drug was found to be 0.9 (with a range of 0.6 to 2.8) hours [FDA Label].; ; The half-life of the active metabolite, ACP-5862, is about 6.9 hours [FDA Label].
DESCRIPTION
Acalabrutinib is an orally available second-generation, selective and irreversible inhibitor of Bruton tyrosine kinase (BTK) , being investigated for its potential antineoplastic activity (in multiple haematologic malignancies and solid tumours), as well as a potential therapy for rheumatoid arthritis. Acalabrutinib covalently bonds to Cysteine-481 in BTK.
(GtoPdb)
DESCRIPTION
Acalabrutinib (ACP-196) is an orally active, irreversible, and highly selective second-generation BTK inhibitor. Acalabrutinib binds covalently to Cys481 in the ATP-binding pocket of BTK. Acalabrutinib demonstrates potent on-target effects and efficacy in mouse models of chronic lymphocytic leukemia (CLL)[1][2]. Acalabrutinib is a click chemistry reagent, itcontains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
PRICE
52
DESCRIPTION
Acalabrutinib is currently indicated for the treatment of adult patients with Mantle Cell Lymphoma (MCL) who have received at least one prior therapy
(PKIDB)
DESCRIPTION
Acalabrutinib is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. It prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. It also plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
(Enamine Bioactive Compounds)
DESCRIPTION
Acalabrutinib (ACP-196), also known as ACP-196, is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
3
Organisms
0
Compound Sets
24
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
CovalentInDB
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
Enamine Bioactive Compounds
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
JUMP-Target 1 Compound Set
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
31
Molecular Weight
465.19
Hydrogen Bond Acceptors
7
Hydrogen Bond Donors
2
Rotatable Bonds
4
Ring Count
5
Aromatic Ring Count
4
cLogP
3.31
TPSA
118.51
Fraction CSP3
0.19
Chiral centers
1.0
Largest ring
6.0
QED
0.45
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
BTK
Indication
mantle cell lymphoma (MCL)
MOA
Bruton's Tyrosine Kinase (BTK) Inhibitor
Pathway
Angiogenesis
Tyrosine Kinase/Adaptors
Protein Tyrosine Kinase/RTK
Therapeutic Class
Antiviral Agents
Recommended Cell Concentration
1 uM
Source data
