kb-NB142-70

Names

[ Name ]:
kb-NB142-70

[Synonym ]:
[1]Benzothieno[2,3-f]-1,4-thiazepin-5(2H)-one, 3,4-dihydro-9-hydroxy-
9-Hydroxy-3,4-dihydro[1]benzothieno[2,3-f][1,4]thiazepin-5(2H)-one
9-hydroxy-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one
kb NB 142-70

Biological Activity

[Description]:

kb NB 142-70 is a potent PKD inhibitor, with IC50s of 28.3, 58.7 and 53.2 nM for PKD1, PKD2, and PKD3, respectively. kb NB 142-70 also has antitumor activity.

[Related Catalog]:

Signaling Pathways >> Apoptosis >> PKD

Research Areas >> Cancer

[Target]

PKD1:28.3 nM (IC50)

PKD3:53.2 nM (IC50)

PKD2:58.7 nM (IC50)

[In Vitro]

kb NB 142-70 is a potent PKD inhibitor, with IC50s of 28.3, 58.7 and 53.2 nM for PKD1, PKD2, and PKD3, respectively. kb NB 142-70 also inhibits Ser916 phosphorylation of PKD1 (IC50, 2.2 ± 0.6 μM) in LNCaP cells. Moreover, kb NB 142-70 is cytotoxic against PC3 cells with an EC50 of 8.025 μM[1]. kb NB 142-70 (0-5 μM) concentration-dependently prevents ANG II-induced phosphorylation of HDAC4 at Ser246 and Ser632, HDAC5 at Ser259 and Ser498, and HDAC7 at Ser155 in IEC-18 cells. In addition, kb NB 142-70 (3.5 μM) also suppresses HDAC4, HDAC5, and HDAC7 phosphorylation in IEC-18 cells stimulated with ANG II for 0-240 min or with vasopressin, lysophosphatidic acid (LPA), or phorbol 12,13-dibutyrate (PDBu)[2].

[Cell Assay]

Briefly, PC3 cells are treated with kb NB 142-70 at 10 μM concentration for 48 h, and then fixed in 70% ice-cold ethanol overnight and labeled with propidium iodide. The labeled cells are analyzed using a FACScan Benchtop Cytometer[1].

[References]

[1]. Lavalle CR, et al. Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility. BMC Chem Biol. 2010 May 5;10:5.

[2]. James Sinnett-Smith, et al. Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling. Am J Physiol Cell Physiol. 2014 May 15; 306(10): C961-C971.

[Related Small Molecules]

1-NM-PP1 | CID755673 | CRT0066101 | CID-2011756

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
601.9±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₁H₉NO₂S₂

[ Molecular Weight ]:
251.325

[ Flash Point ]:
317.8±31.5 °C

[ Exact Mass ]:
251.007462

[ PSA ]:
106.36000

[ LogP ]:
2.39

[ Appearance of Characters ]:
white solid

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.746

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Targeting vascular endothelial growth factor receptor 2 and protein kinase D1 related pathways by a multiple kinase inhibitor in angiogenesis and inflammation related processes in vitro.

PLoS ONE 10(4) , e0124234, (2015)

Emerging evidence suggests that the vascular endothelial growth factor receptor 2 (VEGFR2) and protein kinase D1 (PKD1) signaling axis plays a critical role in normal and pathological angiogenesis and...

PKD1 is downregulated in non-small cell lung cancer and mediates the feedback inhibition of mTORC1-S6K1 axis in response to phorbol ester.

Int. J. Biochem. Cell Biol. 60 , 34-42, (2015)

Protein kinase D1 (PKD1) is increasingly implicated in multiple biological and molecular events that regulate the proliferation or invasiveness in several cancers. However, little is known about the e...

Positive cross talk between protein kinase D and β-catenin in intestinal epithelial cells: impact on β-catenin nuclear localization and phosphorylation at Ser552.

Am. J. Physiol. Cell Physiol. 310 , C542-57, (2016)

Given the fundamental role of β-catenin signaling in intestinal epithelial cell proliferation and the growth-promoting function of protein kinase D1 (PKD1) in these cells, we hypothesized that PKDs me...