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10.1016/j.jbc.2021.100449 http://scihub22266oqcxt.onion/10.1016/j.jbc.2021.100449 33617879!7946438!33617879     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2021 ; 296 (ä): 100449 Nephropedia Template TP {{tp|p=33617879|t=2021. Selective targeting of the inactive state of hematopoietic cell kinase (Hck) with a stable curcumin derivative |pdf=|usr=}}{{33617879}} gab.com Text Selective targeting of the inactive state of hematopoietic cell kinase (Hck) with a stable curcumin derivative JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=33617879 #FOAvip Hck, a Src family nonreceptor tyrosine kinase (SFK), has recently been established as an attractive pharmacological target to improve pulmonary function in COVID-19 patients. Hck inhibitors are also well known for their regulatory role in various malignancies and autoimmune diseases. Curcumin has been previously identified as an excellent DYRK-2 inhibitor, but curcumin's fate is tainted by its instability in the cellular environment. Besides, small molecules targeting the inactive states of a kinase are desirable to reduce promiscuity. Here, we show that functionalization of the 4-arylidene position of the fluorescent curcumin scaffold with an aryl nitrogen mustard provides a stable Hck inhibitor (K(d) = 50 +/- 10 nM). The mustard curcumin derivative preferentially interacts with the inactive conformation of Hck, similar to type-II kinase inhibitors that are less promiscuous. Moreover, the lead compound showed no inhibitory effect on three other kinases (DYRK2, Src, and Abl). We demonstrate that the cytotoxicity may be mediated via inhibition of the SFK signaling pathway in triple-negative breast cancer and murine macrophage cells. Our data suggest that curcumin is a modifiable fluorescent scaffold to develop selective kinase inhibitors by remodeling its target affinity and cellular stability. Twit Text FOAVip Selective targeting of the inactive state of hematopoietic cell kinase (Hck) with a stable curcumin derivative ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=33617879 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33617879 #FOAvip English Wikipedia <ref>{{Cite pmid|33617879}}</ref> Selective targeting of the inactive state of hematopoietic cell kinase (Hck) with a stable curcumin derivative #MMPMID33617879 Chakraborty MP; Bhattacharyya S; Roy S; Bhattacharya I; Das R; Mukherjee A J Biol Chem 2021[Jan]; 296 (ä): 100449 PMID33617879show ga Hck, a Src family nonreceptor tyrosine kinase (SFK), has recently been established as an attractive pharmacological target to improve pulmonary function in COVID-19 patients. Hck inhibitors are also well known for their regulatory role in various malignancies and autoimmune diseases. Curcumin has been previously identified as an excellent DYRK-2 inhibitor, but curcumin's fate is tainted by its instability in the cellular environment. Besides, small molecules targeting the inactive states of a kinase are desirable to reduce promiscuity. Here, we show that functionalization of the 4-arylidene position of the fluorescent curcumin scaffold with an aryl nitrogen mustard provides a stable Hck inhibitor (K(d) = 50 +/- 10 nM). The mustard curcumin derivative preferentially interacts with the inactive conformation of Hck, similar to type-II kinase inhibitors that are less promiscuous. Moreover, the lead compound showed no inhibitory effect on three other kinases (DYRK2, Src, and Abl). We demonstrate that the cytotoxicity may be mediated via inhibition of the SFK signaling pathway in triple-negative breast cancer and murine macrophage cells. Our data suggest that curcumin is a modifiable fluorescent scaffold to develop selective kinase inhibitors by remodeling its target affinity and cellular stability. |*Drug Design[MESH] |Animals[MESH] |Cell Line, Tumor[MESH] |Cloning, Molecular[MESH] |Curcumin/analogs & derivatives/chemical synthesis/*pharmacology[MESH] |Drug Stability[MESH] |Dyrk Kinases[MESH] |Epithelial Cells/*drug effects/enzymology/pathology[MESH] |Escherichia coli/genetics/metabolism[MESH] |Gene Expression[MESH] |Gene Expression Regulation[MESH] |Genetic Vectors/chemistry/metabolism[MESH] |HEK293 Cells[MESH] |HT29 Cells[MESH] |Humans[MESH] |Mice[MESH] |Mitogen-Activated Protein Kinase 1/genetics/metabolism[MESH] |Mitogen-Activated Protein Kinase 3/genetics/metabolism[MESH] |Protein Kinase Inhibitors/chemical synthesis/*pharmacology[MESH] |Protein Serine-Threonine Kinases/genetics/metabolism[MESH] |Protein-Tyrosine Kinases/genetics/metabolism[MESH] |Proto-Oncogene Proteins c-abl/genetics/metabolism[MESH] |Proto-Oncogene Proteins c-hck/*antagonists & inhibitors/chemistry/genetics/metabolism[MESH] |RAW 264.7 Cells[MESH] |Recombinant Proteins/chemistry/genetics/metabolism[MESH] |Structure-Activity Relationship[MESH]Selective targeting of the inactive state of hematopoietic cell kinase(epmc).pdf DeepDyve Pubget Overpricing