Structure-Function Relationships of Covalent and Non-Covalent BTK Inhibitors
Zain, Rula and Vihinen, Mauno LU
(2021)
In Frontiers in Immunology
12.
- Abstract
Low-molecular weight chemical compounds have a longstanding history as drugs. Target specificity and binding efficiency represent major obstacles for small molecules to become clinically relevant. Protein kinases are attractive cellular targets; however, they are challenging because they present one of the largest protein families and share structural similarities. Bruton tyrosine kinase (BTK), a cytoplasmic protein tyrosine kinase, has received much attention as a promising target for the treatment of B-cell malignancies and more recently autoimmune and inflammatory diseases. Here we describe the structural properties and binding modes of small-molecule BTK inhibitors, including irreversible and reversible inhibitors. Covalently... (More)
Low-molecular weight chemical compounds have a longstanding history as drugs. Target specificity and binding efficiency represent major obstacles for small molecules to become clinically relevant. Protein kinases are attractive cellular targets; however, they are challenging because they present one of the largest protein families and share structural similarities. Bruton tyrosine kinase (BTK), a cytoplasmic protein tyrosine kinase, has received much attention as a promising target for the treatment of B-cell malignancies and more recently autoimmune and inflammatory diseases. Here we describe the structural properties and binding modes of small-molecule BTK inhibitors, including irreversible and reversible inhibitors. Covalently binding compounds, such as ibrutinib, acalabrutinib and zanubrutinib, are discussed along with non-covalent inhibitors fenebrutinib and RN486. The focus of this review is on structure-function relationships.
(Less)
- author
- Zain, Rula
and Vihinen, Mauno
LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- acalabrutinib, BTK inhibitors, covalent and non-covalent binding, fenebrutinib, ibrutinib, protein-inhibitor interactions, structure-function relationship, zanubrutinib
- in
- Frontiers in Immunology
- volume
- 12
- article number
- 694853
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85111904264
- pmid:34349760
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2021.694853
- language
- English
- LU publication?
- yes
- id
- 2e143075-23fe-472b-92ac-27ec6e521c67
- date added to LUP
- 2021-09-01 14:37:22
- date last changed
- 2024-06-16 18:07:14
@article{2e143075-23fe-472b-92ac-27ec6e521c67,
abstract = {{<p>Low-molecular weight chemical compounds have a longstanding history as drugs. Target specificity and binding efficiency represent major obstacles for small molecules to become clinically relevant. Protein kinases are attractive cellular targets; however, they are challenging because they present one of the largest protein families and share structural similarities. Bruton tyrosine kinase (BTK), a cytoplasmic protein tyrosine kinase, has received much attention as a promising target for the treatment of B-cell malignancies and more recently autoimmune and inflammatory diseases. Here we describe the structural properties and binding modes of small-molecule BTK inhibitors, including irreversible and reversible inhibitors. Covalently binding compounds, such as ibrutinib, acalabrutinib and zanubrutinib, are discussed along with non-covalent inhibitors fenebrutinib and RN486. The focus of this review is on structure-function relationships.</p>}},
author = {{Zain, Rula and Vihinen, Mauno}},
issn = {{1664-3224}},
keywords = {{acalabrutinib; BTK inhibitors; covalent and non-covalent binding; fenebrutinib; ibrutinib; protein-inhibitor interactions; structure-function relationship; zanubrutinib}},
language = {{eng}},
publisher = {{Frontiers Media S. A.}},
series = {{Frontiers in Immunology}},
title = {{Structure-Function Relationships of Covalent and Non-Covalent BTK Inhibitors}},
url = {{http://dx.doi.org/10.3389/fimmu.2021.694853}},
doi = {{10.3389/fimmu.2021.694853}},
volume = {{12}},
year = {{2021}},
}