SU6656

Last updated
SU6656
SU6656.svg
Names
IUPAC name
(3Z)-N,N-Dimethyl-2-oxo-3-(4,5,6,7-tetrahydro-1H-indol-2-ylmethylidene)-2,3-dihydro-1H-indole-5-sulfonamide
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
  • InChI=1S/C19H21N3O3S/c1-22(2)26(24,25)14-7-8-18-15(11-14)16(19(23)21-18)10-13-9-12-5-3-4-6-17(12)20-13/h7-11,20H,3-6H2,1-2H3,(H,21,23)/b16-10-
  • O=S(=O)(c1cc\2c(cc1)NC(=O)C/2=C/c3cc4c([nH]3)CCCC4)N(C)C
Properties
C19H21N3O3S
Molar mass 371.46 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

SU6656 is a Src family kinase inhibitor developed by the biotechnology company SUGEN Inc (a subsidiary of Pharmacia) in 2000. [1] SU6656 was initially identified as a Src kinase inhibitor by virtue of its ability to reverse an effect that an activated mutant form of Src (hu SRC Y530F) has on the actin cytoskeleton, namely the formation of podosome rosettes, otherwise known as invadopodia. SU6656 was initially published as a Src family kinase inhibitor with selectivity relative to Platelet-derived growth factor receptor Tyrosine kinase. [2] Subsequent studies have confirmed that SU6656 is relatively selective for Src family kinases, but some additional biochemical activities have been identified including: BRSK2, AMPK, Aurora C, Aurora B, CaMKKβ. [3] The inhibition of these kinases in biochemical reactions in vitro does not necessarily indicate that these kinases are targets of SU6656 in cells.

SU6656 has been used primarily as a research tool to investigate the function of Src family kinases in cellular signal transduction processes and biology.

Related Research Articles

Tyrosine kinase Class of enzymes that phosphorylate protein tyrosine residues

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.

Epidermal growth factor receptor Transmembrane protein

The epidermal growth factor receptor is a transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands.

C-Met Mammalian protein found in Homo sapiens

c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the MET gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.

Lck Lymphocyte protein

Lck is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK), it is important for the activation of the T-cell receptor signaling in both naive T cells and effector T cells. The role of the Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the role of the lck varies among the memory T cells subsets. It seems that in mice, in the effector memory T cells (TEM) population, more than 50% of lck is present in a constitutively active conformation, whereas, only less than 20% of lck is present as active form of lck. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

Tropomyosin receptor kinase A

Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the NTRK1 gene.

Insulin-like growth factor 1 receptor Cell surface tyrosine kinase associated receptor, quiche mediates the effects of Igf-1

The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1, which is a polypeptide protein hormone similar in molecular structure to insulin. IGF-1 plays an important role in growth and continues to have anabolic effects in adults – meaning that it can induce hypertrophy of skeletal muscle and other target tissues. Mice lacking the IGF-1 receptor die late in development, and show a dramatic reduction in body mass. This testifies to the strong growth-promoting effect of this receptor.

The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.

Receptor tyrosine kinase Class of enzymes

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.

GRB2

Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.

Adapter molecule crk Protein-coding gene in the species Homo sapiens

Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.

RET proto-oncogene Mammalian protein

The RETproto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor (GDNF) family of extracellular signalling molecules. RET loss of function mutations are associated with the development of Hirschsprung's disease, while gain of function mutations are associated with the development of various types of human cancer, including medullary thyroid carcinoma, multiple endocrine neoplasias type 2A and 2B, pheochromocytoma and parathyroid hyperplasia.

FYN Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.

LYN Mammalian protein found in Homo sapiens

Tyrosine-protein kinase Lyn is a protein that in humans is encoded by the LYN gene.

PTK2 Protein-coding gene in humans

PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes. It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.

HCK Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the HCK gene.

Proto-oncogene tyrosine-protein kinase Src Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src, is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family kinases and is similar to the v-Src gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript variants encoding the same protein have been found for this gene.

TEC (gene)

Tyrosine-protein kinase Tec is a tyrosine kinase that in humans is encoded by the TEC gene. Tec kinase is expressed in hematopoietic, liver, and kidney cells and plays an important role in T-helper cell processes. Tec kinase is the name-giving member of the Tec kinase family, a family of non-receptor protein-tyrosine kinases.

Tyrosine kinase inhibitor Drug

A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia. They have also been used to treat other diseases, such as idiopathic pulmonary fibrosis.

Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs in invertebrates such as flies and worms, and Src homologs exist in organisms as diverse as unicellular choanoflagellates, but the SrcA and SrcB subfamilies are specific to vertebrates. Src family kinases contain six conserved domains: a N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail.

Tyrosine-protein kinase CSK Kinase enzyme that phosphorylates Src-family kinases

Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. This enzyme phosphorylates tyrosine residues located in the C-terminal end of Src-family kinases (SFKs) including SRC, HCK, FYN, LCK, LYN and YES1.

References

  1. ↑ US 6114371,Tang, Peng Cho; Sun, Li& McMahon, Geraldet al.,"3-(cyclohexanoheteroarylidenyl)-2-indolinone protein tyrosine kinase inhibitors",published 1898-09-27, assigned to Sugen Inc.
  2. ↑ Blake, R. A., M. A. Broome; et al. (2000). "SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling". Mol Cell Biol. 20 (23): 9018–9027. doi:10.1128/MCB.20.23.9018-9027.2000. PMC   86555 . PMID   11074000.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ↑ Bain, J., L. Plater; et al. (2007). "The selectivity of protein kinase inhibitors: a further update". Biochem J. 408 (3): 297–315. doi:10.1042/BJ20070797. PMC   2267365 . PMID   17850214.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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