Acting and reacting in life science biotechnologies
Are you working on autophagy,? Or on GPCR de-orphaning? On the MAP kinase pathway or cellular metabolism? Maybe on pathways related to cellular metabolism?
Several compounds are known as modulators of these pathways and research fields and can be used as useful tools to study and characterize specific steps. Nonetheless, it is quite time consuming and expensive to order all these chemicals from different sources. Targeted compound libraries represent a convenient alternative. [Read more…]
Autotaxin (ATX) is a secreted lysophospholipase D involved in the release of the lipid mediator LPA. Many research tools have been developed to study ATX-LPA signaling.  In this post, I invite you to discover a few of them aimed at vizualizing, quantifying or inhibiting the “ATX-LPA” related pathway.
RIPA buffer is one of the most useful protein extraction buffers and maintains most native structures of proteins. Nevertheless, RIPA buffer is not convenient enough to extract membrane proteins and membrane-associated proteins concentrated in lipid raft.
Lipid raft is a highly unique microdomain on the lipid bilayer which contains special lipids, cholesterol and functional proteins. In this layer, lipid raft-enriched proteins are usually insoluble in mild detergent buffers such as 1% Triton X-100 and RIPA buffer. Consequently, it was, up to now, difficult to analyze the functions of this kind of proteins.
Cell-based calcium assays have been a mainstay of GPCR (G protein coupled receptor) drug discovery and signal transduction research since the mid 1990s. However, a calcium readout alone might be ambiguous, because many cellular processes produce calcium. Furthermore, it does not differentiate between signalling pathways routed through the different types of heterotrimeric G proteins. While effects on GPCRs which exhibit effects on Gs proteins lead to an elevated level of the second messaeger cAMP by activating the activity of adenylate cyclase, signalling through Gi proteins inhibits adenylate cyclase and thus leads to a decrease of cAMP. Finally signalling through Gq proteins leads to phospolipase C activation which cleaves Phosphatidylinositol 4,5-bisphosphate (PIP2) to Diacetlyglycerol (DAG) and Inositol trisphosphate (IP3) which leads to an increase in Ca2+ level (for an overview see reference 1).
Dye based methods to measure Ca2+ are very well established, whereas there are no dyes available for most of the other second messengers in these signalling pathways.
That’s why Montana Molecular developed genetically encoded fluorescent biosensors for second messengers such as cAMP, DAG, PIP2, and Ca2+, references 2, 3). [Read more…]
Montelukast is a marketed drug used for asthma treatment and to relieve symptoms of seasonal allergies. It is known to function as a leukotriene receptor antagonist.
Montelukast (Data deposited in or computed by PubChem)
In a recent study in which young and old rats were treated with Montelukast, Maschallinger et al. (1) could show that the drug reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. They could further demonstrate that some of these findings are mediated through an inhibitory effect on the GPR17 receptor.
GPR17 is an orphan G-protein-coupled receptor that is abundant in the CNS, and has been shown to play a key role in regulating oligodendrocyte differentiation and maturation although little has been known about the exact mechanism through which GPR17 influences myelination (2).
The most important result of their study is that cognitive function of old animals could be restored by the treatment with Montelukast. This could be shown in two different behavioral tests. While young rats have not been affected by the drug treatment, Montelukast significantly improved task learning in 20-month old rats. Non-cognitive behaviours such as anxiety-like behaviour, depression-like symptoms, exploration and locomotion as well as changes in body weight have not been affected by Montelukast treatment. Furthermore the authors found that Montelukast reduced microglia reactivity and restored hippocampal neurogenesis in old rats.
These findings might open the door for new potential pharmaceutic applications for Montelukast in treating dementia.
MDL29,951
Focus Biomolecules recently released Montelukast to facilitate GPR17 related research activities. Focus Biomolecules also offer 2 more GPR17 modulators through tebu-bio.
Pranlukast
oligodendrocytes and facilitates further study of this important process.
Interested in these modulators? Please contact us with the form below
(1) J. Maschallinger et al., Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug, Nat Commun. 6, 8466 (2015)
(2) S. Hennen et al.,Decoding signaling and function of the orphan G protein-coupled receptor GPR17 with a small-molecule agonist, Sci Signal. 6, 298 (2013)
In Pharma screening departments there is a strong need for Ca2+ measurement methods.
Why is this?
GPCRs (G Protein Coupled Receptors) are still major targets of pharmaceutical screenings.
Around 30-40% of all drugs on the market are directed against GPCRs.
Drugs have an impact on the GPCR activity and thus the downstream signal transduction cascade. GPCRs are linked to the activity of heterotrimeric G proteins which consist of alpha, beta and gamma subunits. These G proteins have an effect on PhosphoLipase C (PLC) which leads to the release of Inositol Phosphate 3 (IP3) which finally leads to intracellular Ca2+ mobilization (release from the endoplasmic reticulum ) – Ca2+Â finally has effect on a number of further cellular processes.
The fact that GPCR activation always leads to Ca2+mobilization is commonly used to indirectly measure the impact of compounds/drug candicates on GPCRs.
Hence the need for Ca2+ measurement methods, such as the following… [Read more…]