 |
free hosting image hosting hosting reseller online album e-shop famous people |  |
  |
||
|
free hosting image hosting hosting reseller online album e-shop famous people | |
|
||
KT5823 is a semi-synthetic derivative of K525a. It is a potent, selective inhibitor of cGMP-dependent protein kinase (PKG) (in vitro IC50=234nM). KT5823 interferes at the level of the ATP binding site of the catalytic domain of PKG. The PKG are Ser/Thr protein kinase with broad substrate specificity, and expressed in; brain, smooth muscle cells, platelets, juxtaglomerular kidney cells, and endothelial cells. KT5823 triggered apoptotic DNA fragmentation in immortalized uterine epithelial cells, suggesting a regulatory role for PKG in the apoptotic process in these cells.
Chemical
Formula: C29H25N3O5
Molecular Weight: M.W. 495.5
Solubility: Soluble in DMSO and DMF.
CAS Number: CAS [126643-37-6]
1: Mol Hum Reprod. 2003 Dec;9(12):775-83. Related Articles, Links
Guanylyl cyclase inhibitors NS2028 and ODQ and protein kinase G (PKG) inhibitor
KT5823 trigger apoptotic DNA fragmentation in immortalized uterine epithelial
cells: anti-apoptotic effects of basal cGMP/PKG.
Chan SL, Fiscus RR.
Department of Physiology (Faculty of Medicine), Epithelial Cell Biology Research
Centre and Centre for Gerontology and Geriatrics, The Chinese University of Hong
Kong, Shatin, New Territories, Hong Kong, China.
The cGMP/protein kinase G (PKG) signalling pathway, at basal levels, has
anti-apoptotic/pro-survival effects in certain neural cells. The present study
determined apoptosis-regulating effects of basal cGMP/PKG in an immortalized
uterine epithelial cell line, HRE-H9 cells, using two soluble guanylyl cyclase (sGC)
inhibitors, NS2028 and ODQ, and a PKG inhibitor, KT5823. A new quantitative,
ultrasensitive technique using capillary electrophoresis with laser-induced
fluorescent detector (CE-LIF), recently developed in our laboratory, was used to
quantify levels of apoptotic DNA fragmentation. NS2028 and ODQ increased
apoptotic DNA fragmentation by 3.5- and 9-fold respectively, suggesting that
lowering basal cGMP levels causes spontaneous apoptosis. 8-Br-cGMP, a
cell-permeable cGMP analogue that directly activates PKG, reduced ODQ-induced
apoptosis by 81%, indicating that replacement of lowered cGMP with a direct PKG
activator prevents apoptosis. Western blot analysis, using PKG type I (PKG-I)-specific
antibody, indicated that HRE-H9 cells express PKG-I at moderate levels.
Inhibiting basal PKG activity with KT5823 increased apoptotic DNA fragmentation
by 9.8-fold. Overall, the data show that inhibitors of basal sGC and PKG
activities in immortalized uterine epithelial cells cause apoptosis, suggesting
that normal basal levels of cGMP and PKG activity may be necessary to prevent a
spontaneous development of apoptosis in these cells.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 14614039 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: Methods Find Exp Clin Pharmacol. 2003 Jun;25(5):343-7. Related Articles,
Links
Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G
inhibitor.
Miyoshi K, Kawakami N, Horio S, Fukui H.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of
Tokushima, Tokushima, Japan.
The role of various protein kinases in the downregulation of histamine H(1)
receptors was studied by using their inhibitors and activators. Human histamine
H(1) receptors (H(1)Rs) expressed in CHO cells were downregulated by histamine
in a dose- and time-dependent manner, and this downregulation continued to
increase over a 24-h period. KT5823, an inhibitor of protein kinase G,
remarkably but not completely reversed the histamine-induced H(1)R
downregulation over 24 h. HA1004, another inhibitor of protein kinase G, showed
a similar inhibitory effect. However, both 8-Br-cGMP and 8-pCPT-cGMP,
membrane-permeable analogues of cGMP, did not show any effects on H(1)R
downregulation in the absence or presence of histamine. Ro 31-8220, an inhibitor
of protein kinase C (PKC), did not affect histamine-induced downregulation of
H(1)R; nor did phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester.
Similarly, histamine-induced downregulation of H(1)R was unaffected by either
H-89, an inhibitor of protein kinase A, or 8-Br-cAMP, a membrane-permeable
analogue of cAMP. (c) 2003 Prous Science. All rights reserved.
Publication Types:
Comparative Study
PMID: 12851655 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: J Biol Chem. 2000 Oct 27;275(43):33536-41. Related Articles, Links
KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in
intact human platelets and rat mesangial cells.
Burkhardt M, Glazova M, Gambaryan S, Vollkommer T, Butt E, Bader B, Heermeier K,
Lincoln TM, Walter U, Palmetshofer A.
Institute of Clinical Biochemistry and Pathobiochemistry and the Division of
Nephrology, Medical University Clinic Wuerzburg, 97080 Wuerzburg, Germany.
Many signal transduction pathways are mediated by the second messengers cGMP and
cAMP, cGMP- and cAMP-dependent protein kinases (cGK and PKA), phosphodiesterases,
and ion channels. To distinguish among the different cGMP effectors, inhibitors
of cGK and PKA have been developed including the K-252 compound KT5823 and the
isoquinolinesulfonamide H89. KT5823, an in vitro inhibitor of cGK, has also been
used in numerous studies with intact cells to implicate or rule out the
involvement of this protein kinase in a given cellular response. However, the
efficacy and specificity of KT5823 as cGK inhibitor in intact cells or tissues
have never been demonstrated. Here, we analyzed the effects of both KT5823 and
H89 on cyclic-nucleotide-mediated phosphorylation of vasodilator-stimulated
phosphoprotein (VASP) in intact human platelets and rat mesangial cells. These
two cell types both express high levels of cGK. KT5823 inhibited purified cGK.
However, with both intact human platelets and rat mesangial cells, KT5823 failed
to inhibit cGK-mediated serine 157 and serine 239 phosphorylation of VASP
induced by nitric oxide, atrial natriuretic peptide, or the membrane-permeant
cGMP analog, 8-pCPT-cGMP. KT5823 enhanced 8-pCPT-cGMP-stimulated VASP
phosphorylation in platelets and did not inhibit forskolin-stimulated VASP
phosphorylation in either platelets or mesangial cells. In contrast H89, an
inhibitor of both PKA and cGK, clearly inhibited 8-pCPT-cGMP and forskolin-stimulated
VASP phosphorylation in the two cell types. The data indicate that KT5823
inhibits purified cGK but does not affect a cGK-mediated response in the two
different cell types expressing cGK I. These observations indicate that data
that interpret the effects of KT5823 in intact cells as the major or only
criteria supporting the involvement of cGK clearly need to be reconsidered.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 10922374 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Res Commun Chem Pathol Pharmacol. 1991 Oct;74(1):3-14. Related Articles,
Links
KT5823 activates human neutrophils and fails to inhibit cGMP-dependent protein
kinase phosphorylation of vimentin.
Wyatt TA, Pryzwansky KB, Lincoln TM.
Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.
The effectiveness of the cGMP-dependent protein kinase inhibitor, KT5823, was
investigated in human neutrophils. KT5823 did not inhibit the cGMP-dependent
protein kinase mediated in vitro, or in situ phosphorylation of vimentin, a
known substrate for this enzyme in activated neutrophils. In addition, KT5823
was shown to induce dramatic shape changes in neutrophils, suggesting it has an
activating effect upon the cells.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 1666198 [PubMed - indexed for MEDLINE]
This page was made by the students of bioinformatics, the OpenUniversity, BirZeit P.A., as a homework in the Survival in the iJungle. It has no intelectual value whatsoever.
If you think your copyright has been violated, we shall remove the offending content at once. Please eMail to: Abuse17@biochem-openu.cjb.net and start your SUBJECT field with the word Abuse17 (Case sensitive) that it might penetrate our spam protection.
Links of the YOLL itself
We must have at least 100 pages here.
Here come some links to top-rated hrefs, such as Microsoft, wikipedia, Google and Yahoo :google, microsoft, yahoo, wikipedia
Now come links to these of fermentek product pages, that are needy : .the homepage of fermentek, FK506 or tacrolimus, products of Fermentek: staurosporine, K252A, aflatoxin, Sirolimus (Rapamycin)
And other link beggars: