1034297-58-9 Usage
Description
Protein kinase D (PKD) is a serine/threonine protein kinase that is activated by diacylglycerol, commonly downstream of PKC signaling. The three human PKD isoforms target a variety of proteins to alter cell proliferation, survival, invasion, and protein transport. CRT5 is a pyrazine benzamide that prevents activation of all three isoforms of PKD in endothelial cells treated with VEGF (IC50s = 1, 2, and 1.5 nM for PKD1, PKD2, and PKD3, respectively). It has little effect on a panel of additional kinases when given at 1 μM. CRT5 blocks phosphorylation of PKD1 on Ser916 and PKD2 on Ser876, but does not affect PKC-dependent PKD phosphorylation or PKD autophosphorylation. It also decreases VEGF-induced endothelial migration, proliferation, and tubulogenesis.
Uses
CRT5 is used in the characterization of biological effects of a novel protein kinase D inhibitor in endothelial cells.
in vitro
the non-linear regression analysis revealed that ld50 value of crt5 was 17 μm. the biochemical ic50 value of crt5 for pkd1, pkd2 and pkd3 were 1, 2 and 1.5 nm, respectively [1]. crt5 (1 μm) completely inhibited pkd1 and pkd2, but showed little inhibitory effect on the pkc isoforms. crt5 significantly reduced vegf-induced phosphorylation of hsp27 at the position ser82. crt5 significantly reduced the migratory response towards vegf by 42–51%. crt5 decreased the proliferation of control cells not treated with vegf to a less extent. vegf increased huvec tubule formation in a collagen-based assay. crt5 markedly inhibited vegf-induced tubulogenesis [1].
references
[1] evans i m, bagherzadeh a, charles m, et al. characterization of the biological effects of a novel protein kinase d inhibitor in endothelial cells[j]. biochemical journal, 2010, 429(3): 565-572.
Check Digit Verification of cas no
The CAS Registry Mumber 1034297-58-9 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,3,4,2,9 and 7 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1034297-58:
(9*1)+(8*0)+(7*3)+(6*4)+(5*2)+(4*9)+(3*7)+(2*5)+(1*8)=139
139 % 10 = 9
So 1034297-58-9 is a valid CAS Registry Number.
1034297-58-9Relevant articles and documents
PYRIDINE BENZAMIDES AND PYRAZINE BENZAMIDES USED AS PKD INHIBITORS
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Page/Page column 101-102, (2008/12/06)
The present invention pertains generally to the field of therapeutic compounds,. arid more specifically to certain pyridine benzamide and pyrazine benzamide compounds (I) (referred to herein as PDBA and PZBA compounds) which, inter alia, inhibit protein kinase D (PKD) (e.g., PKD1, PKD2, PKD3). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PKD, and in the treatment of diseases and conditions that are mediated by PKD1 that are ameliorated by the inhibition of PKD, etc., including proliferative conditions such as cancer, etc.
