Synthesis and In Vitro Evaluation of Gabapentin Prodrugs that Target the Human Apical Sodium-Dependent Bile Acid Transporter (hASBT)

2011 ◽  
Vol 100 (3) ◽  
pp. 1184-1195 ◽  
Author(s):  
Rana Rais ◽  
Steven Fletcher ◽  
James E. Polli
Keyword(s):  
Bile Acid ◽  
In Vitro Evaluation ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Acid Transporter

Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid

1997 ◽  
Vol 113 (5) ◽  
pp. 1599-1608 ◽  
Author(s):  
RT Stravitz ◽  
AJ Sanyal ◽  
WM Pandak ◽  
ZR Vlahcevic ◽  
JW Beets ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Messenger Rna ◽  
Rat Ileum ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Acid Transporter

scholarly journals Hepatitis D Virus Entry Inhibitors Based on Repurposing Intestinal Bile Acid Reabsorption Inhibitors

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 666
Author(s):  
Michael Kirstgen ◽  
Kira Alessandra Alicia Theresa Lowjaga ◽  
Simon Franz Müller ◽  
Nora Goldmann ◽  
Felix Lehmann ◽  
...  
Keyword(s):  
Bile Acid ◽  
Taurocholic Acid ◽  
Hek293 Cells ◽  
Acid Uptake ◽  
Hepatitis D ◽  
Entry Inhibitors ◽  
Ic50 Values ◽  
Bile Acid Transporter ◽  
Acid Transporter

Identification of Na+/taurocholate co-transporting polypeptide (NTCP) as high-affinity hepatic entry receptor for the Hepatitis B and D viruses (HBV/HDV) opened the field for target-based development of cell-entry inhibitors. However, most of the HBV/HDV entry inhibitors identified so far also interfere with the physiological bile acid transporter function of NTCP. The present study aimed to identify more virus-selective inhibitors of NTCP by screening of 87 propanolamine derivatives from the former development of intestinal bile acid reabsorption inhibitors (BARIs), which interact with the NTCP-homologous intestinal apical sodium-dependent bile acid transporter (ASBT). In NTCP-HEK293 cells, the ability of these compounds to block the HBV/HDV-derived preS1-peptide binding to NTCP (virus receptor function) as well as the taurocholic acid transport via NTCP (bile acid transporter function) were analyzed in parallel. Hits were subsequently validated by performing in vitro HDV infection experiments in NTCP-HepG2 cells. The most potent compounds S985852, A000295231, and S973509 showed in vitro anti-HDV activities with IC50 values of 15, 40, and 70 µM, respectively, while the taurocholic acid uptake inhibition occurred at much higher IC50 values of 24, 780, and 490 µM, respectively. In conclusion, repurposing of compounds from the BARI class as novel HBV/HDV entry inhibitors seems possible and even enables certain virus selectivity based on structure-activity relationships.

Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum

1996 ◽  
Vol 271 (2) ◽  
pp. G377-G385 ◽  
Author(s):  
D. M. Christie ◽  
P. A. Dawson ◽  
S. Thevananther ◽  
B. L. Shneider
Keyword(s):  
Bile Acid ◽  
Rat Kidney ◽  
Membrane Vesicles ◽  
Mrna Levels ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Old Rats ◽  
Acid Transporter ◽  
The Difference ◽  
And Function

An apical sodium-dependent bile acid transporter (ASBT) has recently been cloned and characterized in the rat ileum. Northern and Western blotting revealed both the ASBT mRNA and protein in rat kidney. The coding sequence of the kidney transcript was found to be identical to the previously cloned ileal ASBT. Indirect immunofluorescence studies localized the ASBT protein to the apical membrane of the renal proximal convoluted tubule. Kinetic analysis of sodium-dependent taurocholate uptake using membrane vesicles revealed a similar Michaelis-Menten constant value for taurocholate in the kidney and intestine. ASBT protein and function were present in the kidney but not the ileum from 7-day-old rats. On postnatal day 7, there was a sevenfold increase in ASBT steady-state mRNA levels in the kidney relative to the ileum, yet nuclear run-on assays revealed that the nascent transcription rates at this age were virtually the same. This suggests that the difference in the neonatal expression of the ASBT gene in the kidney and ileum may be in part due to differences in mRNA stability.

Inhibitors of the Apical Sodium-Dependent Bile Acid Transporter (ASBT) as Promising Drugs

2021 ◽  
Vol 15 (1) ◽  
pp. 16-26
Author(s):  
E. E. Saveleva ◽  
E. S. Tyutrina ◽  
T. Nakanishi ◽  
I. Tamai ◽  
A. B. Salmina
Keyword(s):  
Bile Acid ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Acid Transporter
Sign in / Sign up

Export Citation Format

Share Document