CHIR99021

Last updated
CHIR99021
CHIR99021 structure.png
Names
IUPAC name
6-((2-((4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-yl)amino)ethyl)amino)nicotinonitrile
Identifiers
3D model (JSmol)
ECHA InfoCard 100.236.922 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
Properties
C25H18Cl2N8
Molar mass 501.38 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

CHIR99021 is a chemical compound which acts as an inhibitor of the enzyme GSK-3. [1] It has proved useful for applications in molecular biology involving the transformation of one cell type to another. [2] [3]

A mixture of CHIR99021 and valproic acid is claimed to increase the proliferation of inner ear stem cells, potentially allowing regrowth of the hair cells which are important for hearing, and are lost through chronic exposure to loud noises or as part of the aging process. [4] [5]

See also

Related Research Articles

Plant hormone Chemical compounds that regulate plant growth and development

Plant hormones are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, from embryogenesis, the regulation of organ size, pathogen defense, stress tolerance and through to reproductive development. Unlike in animals each plant cell is capable of producing hormones. Went and Thimann coined the term "phytohormone" and used it in the title of their 1937 book.

Drug discovery

In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.

GSK-3

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS), GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways. In mammals, including humans, GSK-3 exists in two isoforms encoded by two paralogous genes GSK-3α (GSK3A) and GSK-3β (GSK3B). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, and bipolar disorder.

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia.

Induced pluripotent stem cell Pluripotent stem cell generated directly from a somatic cell

Induced pluripotent stem cells are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka’s lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert somatic cells into pluripotent stem cells. He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."

Telomerase reverse transcriptase

Telomerase reverse transcriptase is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.

GSK3B

Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene. In mice, the enzyme is encoded by the GSK-3β gene. Abnormal regulation and expression of GSK3β is associated with an increased susceptibility towards bipolar disorder.

EZH2

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme encoded by EZH2 gene, that participates in histone methylation and, ultimately, transcriptional repression. EZH2 catalyzes the addition of methyl groups to histone H3 at lysine 27, by using the cofactor S-adenosyl-L-methionine. Methylation activity of EZH2 facilitates heterochromatin formation thereby silences gene function. Remodeling of chromosomal heterochromatin by EZH2 is also required during cell mitosis.

Inte:Ligand was founded in Maria Enzersdorf, Lower Austria (Niederösterreich) in 2003. They established the company headquarters on Mariahilferstrasse in Vienna, Austria that same year.

Carmofur

Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative of fluorouracil, being a lypophilic-masked analog of 5-FU that can be administered orally.

Mesenchymal stem cell Multipotent, non-hematopoietic adult stem cells present in multiple tissues

Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes and adipocytes.

SB-431542

SB-431542 is a drug candidate developed by GlaxoSmithKline (GSK) as an inhibitor of the activin receptor-like kinase (ALK) receptors, ALK5, ALK4 and ALK7. However, it is not an inhibitor of anaplastic lymphoma kinase.

Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

JQ1

JQ1 is a thienotriazolodiazepine and a potent inhibitor of the BET family of bromodomain proteins which include BRD2, BRD3, BRD4, and the testis-specific protein BRDT in mammals. BET inhibitors structurally similar to JQ1 are being tested in clinical trials for a variety of cancers including NUT midline carcinoma. It was developed by the James Bradner laboratory at Brigham and Women's Hospital and named after chemist Jun Qi. The chemical structure was inspired by patent of similar BET inhibitors by Mitsubishi Tanabe Pharma [WO/2009/084693]. Structurally it is related to benzodiazepines. While widely used in laboratory applications, JQ1 is not itself being used in human clinical trials because it has a short half life.

Protein <i>O</i>-GlcNAc transferase

Protein O-GlcNAc transferase also known as OGT is an enzyme that in humans is encoded by the OGT gene. OGT catalyzes the addition of the O-GlcNAc post-translational modification to proteins.

Rho kinase inhibitors are a series of compounds that target rho kinase (ROCK). 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.

GSK-4112

GSK-4112 is an experimental drug that was developed by GlaxoSmithKline as an agonist of Rev-ErbAα. It is used for studying regulation of the circadian rhythm and its influence on diverse processes such as adipogenesis, regulation of bone density, and inflammation.

Thiazovivin

Thiazovivin is a drug which acts as a potent and selective inhibitor of the enzyme Rho kinase. It is used alongside a cocktail of other growth factors and modulators in cell culture techniques for the generation of induced pluripotent stem cells, which can then be used for a wide variety of applications.

References

  1. An WF, Germain AR, Bishop JA, Nag PP, Metkar S, Ketterman J, et al. (16 April 2012). "Discovery of Potent and Highly Selective Inhibitors of GSK3b". Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US). PMID   23658955.
  2. Singh VK, Kumar N, Kalsan M, Saini A, Chandra R (2015). "Mechanism of Induction: Induced Pluripotent Stem Cells (iPSCs)". Journal of Stem Cells. 10 (1): 43–62. PMID   26665937.
  3. Takeda Y, Harada Y, Yoshikawa T, Dai P (June 2018). "Chemical compound-based direct reprogramming for future clinical applications". Bioscience Reports. 38 (3). doi:10.1042/BSR20171650. PMC   5938430 . PMID   29739872.
  4. US 2017226477,Karp JM, Yin X, Succi MD, Langer RS,"Compositions and methods for epithelial stem cell expansion and culture",published 10 August 2017, assigned to Massachusetts Institute of Technologyand The Brigham and Women's Hospital, Inc.
  5. McLean WJ, Yin X, Lu L, Lenz DR, McLean D, Langer R, et al. (February 2017). "Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells". Cell Reports. 18 (8): 1917–1929. doi:10.1016/j.celrep.2017.01.066. PMC   5395286 . PMID   28228258.