Y-27632

Last updated
Y-27632
Y-27632.svg
Names
IUPAC name
(1R,4r)-4-((R)-1-Aminoethyl)-N-(pyridin-4-yl)cyclohexanecarboxamide
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.149.247 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C14H21N3O/c1-10(15)11-2-4-12(5-3-11)14(18)17-13-6-8-16-9-7-13/h6-12H,2-5,15H2,1H3,(H,16,17,18)/t10-,11-,12-/m1/s1 Yes check.svgY
    Key: IYOZTVGMEWJPKR-IJLUTSLNSA-N Yes check.svgY
  • InChI=1/C14H21N3O/c1-10(15)11-2-4-12(5-3-11)14(18)17-13-6-8-16-9-7-13/h6-12H,2-5,15H2,1H3,(H,16,17,18)/t10-,11-,12-/m1/s1
    Key: IYOZTVGMEWJPKR-IJLUTSLNBP
  • O=C([C@H]1CC[C@@]([C@H](N)C)([H])CC1)NC2=CC=NC=C2
Properties
C14H21N3O
Molar mass 247.342 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Y-27632 is a biochemical tool used in the study of the rho-associated protein kinase (ROCK) signaling pathways. [1] Y-27632 selectively inhibits p160ROCK, although it does inhibit other protein kinases such as PKCs at higher concentrations. [2]

It has been studied for its effects on corneal endothelial cells (CECs) [3] and cardiac stem cells (CSCs). [4]

The substance has been used as part of a chemical cocktail to turn old and senescent human cells back into young ones (as measured by transcriptomic age), without turning them all the way back into undifferentiated stem cells. [5]

A mixture of methylcellulose (1%), ethylene glycol (10%), dimethyl sulfoxide (10%), and Y-27632 (10 μM), termed MEDY, has been shown to be an effective cryopreservation reagent for brain tissue, enabling tissue to resume growth and function after freezing using liquid nitrogen. [6]

Related Research Articles

<span class="mw-page-title-main">Myosin light-chain kinase</span> Class of kinase enzymes

Myosin light-chain kinase also known as MYLK or MLCK is a serine/threonine-specific protein kinase that phosphorylates a specific myosin light chain, namely, the regulatory light chain of myosin II.

p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation, apoptosis and autophagy. Persistent activation of the p38 MAPK pathway in muscle satellite cells due to ageing, impairs muscle regeneration.

<span class="mw-page-title-main">GDF2</span> Protein-coding gene in the species Homo sapiens

Growth differentiation factor 2 (GDF2) also known as bone morphogenetic protein (BMP)-9 is a protein that in humans is encoded by the GDF2 gene. GDF2 belongs to the transforming growth factor beta superfamily.

mir-19 microRNA precursor family

There are 89 known sequences today in the microRNA 19 (miR-19) family but it will change quickly. They are found in a large number of vertebrate species. The miR-19 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. Within the human and mouse genome there are three copies of this microRNA that are processed from multiple predicted precursor hairpins:

<span class="mw-page-title-main">CDC42</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog is a protein that in humans is encoded by the CDC42 gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

<span class="mw-page-title-main">RAC1</span> Protein-coding gene in humans

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

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

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

<span class="mw-page-title-main">PAK1</span> Mammalian protein found in Homo sapiens

Serine/threonine-protein kinase PAK 1 is an enzyme that in humans is encoded by the PAK1 gene.

<span class="mw-page-title-main">ROCK1</span> Protein

ROCK1 is a protein serine/threonine kinase also known as rho-associated, coiled-coil-containing protein kinase 1. Other common names are ROKβ and P160ROCK. ROCK1 is a major downstream effector of the small GTPase RhoA and is a regulator of the actomyosin cytoskeleton which promotes contractile force generation. ROCK1 plays a role in cancer and in particular cell motility, metastasis, and angiogenesis.

<span class="mw-page-title-main">Cyclin-dependent kinase 7</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene.

<span class="mw-page-title-main">PAK2</span> Mammalian protein found in Homo sapiens

Serine/threonine-protein kinase PAK 2 is an enzyme that in humans is encoded by the PAK2 gene.

<span class="mw-page-title-main">S1PR1</span> Protein and coding gene in humans

Sphingosine-1-phosphate receptor 1, also known as endothelial differentiation gene 1 (EDG1) is a protein that in humans is encoded by the S1PR1 gene. S1PR1 is a G-protein-coupled receptor which binds the bioactive signaling molecule sphingosine 1-phosphate (S1P). S1PR1 belongs to a sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). S1PR1 was originally identified as an abundant transcript in endothelial cells and it has an important role in regulating endothelial cell cytoskeletal structure, migration, capillary-like network formation and vascular maturation. In addition, S1PR1 signaling is important in the regulation of lymphocyte maturation, migration and trafficking.

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

Tyrosine-protein kinase receptor UFO is a protein that in human is encoded by the AXL gene. The gene was initially designated as UFO, in allusion to the unidentified function of this protein. However, in the years since its discovery, research into AXL's expression profile and mechanism has made it an increasingly attractive target, especially for cancer therapeutics. In recent years, AXL has emerged as a key facilitator of immune escape and drug-resistance by cancer cells, leading to aggressive and metastatic cancers.

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

RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.

<span class="mw-page-title-main">MAP4K4</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) – also known as hepatocyte progenitor kinase-like/germinal center kinase-like kinase (HGK) and Nck-interacting kinase (NIK) – is an enzyme, specifically a serine/threonine (S/T) kinase encoded by the MAP4K4 gene in humans.

mIRN21 Non-coding RNA in the species Homo sapiens

microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA that is encoded by the MIR21 gene.

Fasudil (INN) is a potent Rho-kinase inhibitor and vasodilator. Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke patients. It has been found to be effective for the treatment of pulmonary hypertension. It has been demonstrated that fasudil could improve memory in normal mice, identifying the drug as a possible treatment for age-related or neurodegenerative memory loss.

<span class="mw-page-title-main">Rho-associated protein kinase</span>

Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton.

<span class="mw-page-title-main">Rho kinase inhibitor</span>

Rho-kinase inhibitors are a series of compounds that target rho kinase (ROCK) and inhibit the ROCK pathway. Clinical trials have found that inhibition of the ROCK pathway contributes to the cardiovascular benefits of statin therapy. Furthermore, ROCK inhibitors may have clinical applications for anti-erectile dysfunction, antihypertension, and tumor metastasis inhibition. More recently they have been studied for the treatment of glaucoma and as a therapeutic target for the treatment of cardiovascular diseases, including ischemic stroke. While statin therapy has been demonstrated to reduce the risk of major cardiovascular events, including ischemic stroke, the interplay between the ROCK pathway and statin therapy to treat and prevent strokes in older adults has not yet been proven.

Ripasudil, a derivative of fasudil, is a rho kinase inhibitor drug used for the treatment of glaucoma and ocular hypertension.

References

  1. Uehata, Masayoshi (1999). "Y-27632. Selective probe of ROCK/Rho-kinase". Jikken Igaku. 17 (7): 850–855.
  2. Uehata, M; Ishizaki, T; Satoh, H; Ono, T; Kawahara, T; Morishita, T; Tamakawa, H; Yamagami, K; et al. (1997). "Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension". Nature. 389 (6654): 990–4. Bibcode:1997Natur.389..990U. doi:10.1038/40187. PMID   9353125. S2CID   4419556.
  3. Peh, Gary S. L.; Adnan, Khadijah; George, Benjamin L.; Ang, Heng-Pei; Seah, Xin-Yi; Tan, Donald T.; Mehta, Jodhbir S. (2015-03-16). "The effects of Rho-associated kinase inhibitor Y-27632 on primary human corneal endothelial cells propagated using a dual media approach". Scientific Reports. 5: 9167. Bibcode:2015NatSR...5E9167P. doi:10.1038/srep09167. ISSN   2045-2322. PMC   4387913 . PMID   25823914.
  4. Kan, Lijuan; Smith, Aubrie; Chen, Miao; Ledford, Benjamin T.; Fan, Huimin; Liu, Zhongmin; He, Jia-Qiang (2015-12-08). "Rho-Associated Kinase Inhibitor (Y-27632) Attenuates Doxorubicin-Induced Apoptosis of Human Cardiac Stem Cells". PLOS ONE. 10 (12): e0144513. Bibcode:2015PLoSO..1044513K. doi: 10.1371/journal.pone.0144513 . ISSN   1932-6203. PMC   4672899 . PMID   26645568.
  5. Yang, Jae-Hyun; Petty, Christopher A.; Dixon-McDougall, Thomas; Lopez, Maria Vina; Tyshkovskiy, Alexander; Maybury-Lewis, Sun; Tian, Xiao; Ibrahim, Nabilah; Chen, Zhili; Griffin, Patrick T.; Arnold, Matthew; Li, Jien; Martinez, Oswaldo A.; Behn, Alexander; Rogers-Hammond, Ryan (2023-07-12). "Chemically induced reprogramming to reverse cellular aging". Aging. 15 (13): 5966–5989. doi:10.18632/aging.204896. ISSN   1945-4589. PMC   10373966 . PMID   37437248.
  6. Xue, Weiwei; Li, Huijuan; Xu, Jinhong; Yu, Xiao; Liu, Linlin; Liu, Huihui; Zhao, Rui; Shao, Zhicheng (2024). "Effective cryopreservation of human brain tissue and neural organoids". Cell Reports Methods. 4 (5). doi: 10.1016/j.crmeth.2024.100777 . PMC   11133841 . PMID   38744289.