Yoda1

Last updated
Yoda1
Yoda1 structure.png
Names
Preferred IUPAC name
2-(5-{[(2,6-Dichlorophenyl)methyl]sulfanyl}-1,3,4-thiadiazol-2-yl)pyrazine
Identifiers
3D model (JSmol)
ChEBI
PubChem CID
UNII
  • ClC1=C(CSC2=NN=C(C3=NC=CN=C3)S2)C(Cl)=CC=C1
Properties
C13H8Cl2N4S2
Molar mass 355.27 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Yoda1 is a chemical compound which is the first agonist developed for the mechanosensitive ion channel PIEZO1. This protein is involved in regulation of blood pressure and red blood cell volume, and Yoda1 is used in scientific research in these areas. [1] [2] [3] [4] [5]

Piezo1 channels repress group 2 innate lymphoid cell (ILC2)–driven type 2 inflammation in the lungs. Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation and attenuates the development of bronchial hyperresponsiveness. Piezo1 activation with Yoda1 treatment could become a novel therapeutic approach for the treatment of ILC2-driven allergic asthma. [6]

See also

Related Research Articles

<span class="mw-page-title-main">Thromboxane receptor</span> Mammalian protein found in Homo sapiens

The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the TBXA2R gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid receptor cloned. The TP receptor derives its name from its preferred endogenous ligand thromboxane A2.

<span class="mw-page-title-main">TRPV1</span> Human protein for regulating body temperature

The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. Fatty acid metabolites with affinity for this receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA). The function of TRPV1 is detection and regulation of body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception). In primary afferent sensory neurons, it cooperates with TRPA1 to mediate the detection of noxious environmental stimuli.

<span class="mw-page-title-main">TRPA1</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the TRPA1 gene.

<span class="mw-page-title-main">TRPV4</span> Protein-coding gene in humans

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

<span class="mw-page-title-main">TRPM3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.

<span class="mw-page-title-main">Protease-activated receptor 2</span> Protein-coding gene in the species Homo sapiens

Protease activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is a protein that in humans is encoded by the F2RL1 gene. PAR2 modulates inflammatory responses, obesity, metabolism, cancers and acts as a sensor for proteolytic enzymes generated during infection. In humans, we can find PAR2 in the stratum granulosum layer of epidermal keratinocytes. Functional PAR2 is also expressed by several immune cells such as eosinophils, neutrophils, monocytes, macrophages, dendritic cells, mast cells and T cells.

<span class="mw-page-title-main">Free fatty acid receptor 1</span> Protein-coding gene in the species Homo sapiens

Free fatty acid receptor 1 (FFAR1), also known as G-protein coupled receptor 40 (GPR40), is a rhodopsin-like G-protein coupled receptor that is coded by the FFAR1 gene. This gene is located on the short arm of chromosome 19 at position 13.12. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR1 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes at least three other FFARs viz., FFAR2, FFAR3, and FFAR4. FFARs bind and thereby are activated by certain fatty acids.

<span class="mw-page-title-main">Free fatty acid receptor 4</span> Protein-coding gene in the species Homo sapiens

Free Fatty acid receptor 4 (FFAR4), also termed G-protein coupled receptor 120 (GPR120), is a protein that in humans is encoded by the FFAR4 gene. This gene is located on the long arm of chromosome 10 at position 23.33. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR4 is a rhodopsin-like GPR in the broad family of GPRs which in humans are encoded by more than 800 different genes. It is also a member of a small family of structurally and functionally related GPRs that include at least three other free fatty acid receptors (FFARs) viz., FFAR1, FFAR2, and FFAR3. These four FFARs bind and thereby are activated by certain fatty acids.

Prostaglandin EP<sub>2</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin E2 receptor 2, also known as EP2, is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the human gene PTGER2: it is one of four identified EP receptors, the others being EP1, EP3, and EP4, which bind with and mediate cellular responses to PGE2 and also, but with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP has been implicated in various physiological and pathological responses.

<span class="mw-page-title-main">Prostacyclin receptor</span> Mammalian protein found in Homo sapiens

The Prostacyclin receptor, also termed the prostaglandin I2 receptor or just IP, is a receptor belonging to the prostaglandin (PG) group of receptors. IP binds to and mediates the biological actions of prostacyclin (also termed Prostaglandin I2, PGI2, or when used as a drug, epoprostenol). IP is encoded in humans by the PTGIR gene. While possessing many functions as defined in animal model studies, the major clinical relevancy of IP is as a powerful vasodilator: stimulators of IP are used to treat severe and even life-threatening diseases involving pathological vasoconstriction.

Mechanosensitive channels (MSCs), mechanosensitive ion channels or stretch-gated ion channels are membrane proteins capable of responding to mechanical stress over a wide dynamic range of external mechanical stimuli. They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. They are the sensors for a number of systems including the senses of touch, hearing and balance, as well as participating in cardiovascular regulation and osmotic homeostasis (e.g. thirst). The channels vary in selectivity for the permeating ions from nonselective between anions and cations in bacteria, to cation selective allowing passage Ca2+, K+ and Na+ in eukaryotes, and highly selective K+ channels in bacteria and eukaryotes.

<span class="mw-page-title-main">PIEZO1</span> Protein-coding gene in the species Homo sapiens

PIEZO1 is a mechanosensitive ion channel protein that in humans is encoded by the gene PIEZO1. PIEZO1 and its close homolog PIEZO2 were cloned in 2010, using an siRNA-based screen for mechanosensitive ion channels.

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.

<span class="mw-page-title-main">PIEZO2</span>

Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene. It has a homotrimeric structure, with three blades curving into a nano-dome, with a diameter of 28 nanometers.

<span class="mw-page-title-main">ILC2</span>

ILC2 cells, or type 2 innate lymphoid cells are a type of innate lymphoid cell. Not to be confused with the ILC. They are derived from common lymphoid progenitor and belong to the lymphoid lineage. These cells lack antigen specific B or T cell receptor because of the lack of recombination activating gene. ILC2s produce type 2 cytokines and are involved in responses to helminths, allergens, some viruses, such as influenza virus and cancer.

<span class="mw-page-title-main">Type 3 innate lymphoid cells</span>

Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.

<span class="mw-page-title-main">Wasabi receptor toxin</span>

Wasabi receptor toxin (WaTx) is the active component of the venom of the Australian black rock scorpion Urodacus manicatus. WaTx targets TRPA1, also known as the wasabi receptor or irritant receptor. WaTx is a cell-penetrating toxin that stabilizes the TRPA1 channel open state while reducing its Ca2+-permeability, thereby eliciting pain and pain hypersensitivity without the neurogenic inflammation that typically occurs in other animal toxins.

<span class="mw-page-title-main">Ardem Patapoutian</span> Molecular biologist, neuroscientist, and Nobel laureate 2021

Ardem Patapoutian is a Lebanese-American molecular biologist, neuroscientist, and Nobel Prize laureate of Armenian descent. He is known for his work in characterizing the PIEZO1, PIEZO2, and TRPM8 receptors that detect pressure, menthol, and temperature. Patapoutian is a neuroscience professor and Howard Hughes Medical Institute investigator at Scripps Research in La Jolla, California. In 2021, he won the Nobel Prize in Physiology or Medicine jointly with David Julius.

<span class="mw-page-title-main">Jedi2</span> Chemical compound

Jedi2 is a chemical compound which acts as an agonist for the mechanosensitive ion channel PIEZO1, and is used in research into the function of touch perception.

<span class="mw-page-title-main">Jedi1</span> Chemical compound

Jedi1 is a chemical compound which acts as an agonist for the mechanosensitive ion channel PIEZO1, and is used in research into the function of touch perception.

References

  1. Syeda, Ruhma; Xu, Jie; Dubin, Adrienne E.; Coste, Bertrand; Mathur, Jayanti; Huynh, Truc; Matzen, Jason; Lao, Jianmin; Tully, David C.; Engels, Ingo H.; Petrassi, H. Michael; Schumacher, Andrew M.; Montal, Mauricio; Bandell, Michael; Patapoutian, Ardem (2015). "Chemical activation of the mechanotransduction channel Piezo1". eLife. 4: e07369. doi: 10.7554/eLife.07369 . PMC   4456433 . PMID   26001275. S2CID   2652667 .
  2. Cahalan, Stuart M.; Lukacs, Viktor; Ranade, Sanjeev S.; Chien, Shu; Bandell, Michael; Patapoutian, Ardem (2015). "Piezo1 links mechanical forces to red blood cell volume". eLife. 4: e07370. doi: 10.7554/eLife.07370 . PMC   4456639 . PMID   26001274. S2CID   15018525 .
  3. Wang, ShengPeng; Chennupati, Ramesh; Kaur, Harmandeep; Iring, Andras; Wettschureck, Nina; Offermanns, Stefan (2016). "Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release". Journal of Clinical Investigation. 126 (12): 4527–4536. doi: 10.1172/JCI87343 . PMC   5127677 . PMID   27797339. S2CID   38263363 .
  4. Rapetti-Mauss, Raphaël; Picard, Véronique; Guitton, Corinne; Ghazal, Khaldoun; Proulle, Valérie; Badens, Catherine; Soriani, Olivier; Garçon, Loïc; Guizouarn, Hélène (2017). "Red blood cell Gardos channel (KCNN4): The essential determinant of erythrocyte dehydration in hereditary xerocytosis". Haematologica. 102 (10): e415–e418. doi: 10.3324/haematol.2017.171389 . PMC   5622875 . PMID   28619848. S2CID   31756119 .
  5. Gnanasambandam, R.; Gottlieb, P. A.; Sachs, F. (2017). "The Kinetics and the Permeation Properties of Piezo Channels". In Gottlieb, Philip A. (ed.). Piezo Channels. Current Topics in Membranes. Vol. 79. Academic Press. pp. 275–307. doi:10.1016/bs.ctm.2016.11.004. ISBN   978-0-12-809389-4. PMID   28728821. S2CID   3743286.
  6. Hurrell, B. P., Shen, S., Li, X., Sakano, Y., Kazemi, M. H., Quach, C., ... & Akbari, O. (2024). "Piezo1 channels restrain ILC2s and regulate the development of airway hyperreactivity". Journal of Experimental Medicine, 221(5), e20231835. PMID   38530239 PMC   10965393 (available on 2024-09-26) doi : 10.1084/jem.20231835