SB-431542 is a drug candidate developed by
GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...
(GSK) as an
inhibitor
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
of the
activin receptor-like kinase (ALK)
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
s,
ALK5
Transforming growth factor beta receptor I (activin A receptor type II-like kinase, 53kDa) is a membrane-bound TGF beta receptor protein of the TGF-beta receptor family for the Transforming growth factor beta, TGF beta superfamily of signaling lig ...
,
ALK4 and
ALK7
The activin A receptor also known as ACVR1C or ALK-7 is a protein that in humans is encoded by the ACVR1C gene. ACVR1C is a type I receptor for the TGFB family of signaling molecules.
ACVR1C transduces signals of Nodal. Nodal binds to ACVR2B and ...
.
[ However, it is ''not'' an inhibitor of ]anaplastic lymphoma kinase
Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ''ALK'' gene.
Identification
Anaplastic lymphoma kinase (ALK) was originally dis ...
(which are commonly known as ALK inhibitor
ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4- ALK translocation. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involved ...
s).
In-vitro studies
While SB-431542 has not proved directly useful for any clinical application, it is used for several applications in molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
. It suppresses the TGF-beta
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
-induced proliferation of osteosarcoma cells in humans.astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
s into neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s. It is also commonly used for immunological studies, for instance as a TGF-β inhibitor to facilitate the generation of dendritic cells
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
from peripheral blood monocytes
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...
.
References
{{TGFβ receptor superfamily modulators
Protein kinase inhibitors
Imidazoles
Benzodioxoles
Carboxamides