scholarly journals Synthesis of a Human Urate Transporter-1 Inhibitor, an Arginine Vasopressin Antagonist, and a 17β-Hydroxysteroid Dehydrogenase Type-3 Inhibitor, Using Ring-Expansion of Cyclic Ketoximes with DIBALH

2014 ◽  
Vol 62 (4) ◽  
pp. 354-363 ◽  
Author(s):  
Hidetsura Cho ◽  
Yusuke Iwama ◽  
Kentaro Okano ◽  
Hidetoshi Tokuyama
1987 ◽  
Vol 112 (3) ◽  
pp. 439-442 ◽  
Author(s):  
H. Vilhardt ◽  
S. Lundin

ABSTRACT Using implanted minipumps it was shown over a period of 7 days that the vasopressin antagonist, 1-deamino-pentamethylene-2-d-Phe-4-Ile-arginine vasopressin, caused increased diuresis in normal rats and reversed vasopressin- or oxytocin-induced antidiuresis in Brattleboro rats. When the antagonist was infused alone in Brattleboro rats it induced a marked antidiuretic response, indicating that the analogue also possessed agonistic properties. The agonist action could not be demonstrated in anaesthetized, hydrated normal rats. In these animals the analogue behaved as a pure antagonist. It is concluded that analogues which behave as antagonists in one test model may display agonistic properties under different experimental conditions. J. Endocr. (1987) 112, 439–442


2015 ◽  
Vol 30 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Aisha Al-Sinani ◽  
Waad-Allah Mula-Abed ◽  
Manal Al-Kindi ◽  
Ghariba Al-Kusaibi ◽  
Hanan Al-Azkawi ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171871 ◽  
Author(s):  
Lucie Carolle Kenmogne ◽  
Jenny Roy ◽  
René Maltais ◽  
Mélanie Rouleau ◽  
Bertrand Neveu ◽  
...  

2016 ◽  
Vol 473 (8) ◽  
pp. 1037-1046 ◽  
Author(s):  
Bo Zhang ◽  
Xiao-Jian Hu ◽  
Xiao-Qiang Wang ◽  
Jean-François Thériault ◽  
Dao-Wei Zhu ◽  
...  

Human 3α-HSD3 (3α-hydroxysteroid dehydrogenase type 3) plays an essential role in the inactivation of the most potent androgen 5α-DHT (5α-dihydrotestosterone). The present study attempts to obtain the important structure of 3α-HSD3 in complex with 5α-DHT and to investigate the role of 3α-HSD3 in breast cancer cells. We report the crystal structure of human 3α-HSD3·NADP+·A-dione (5α-androstane-3,17-dione)/epi-ADT (epiandrosterone) complex, which was obtained by co-crystallization with 5α-DHT in the presence of NADP+. Although 5α-DHT was introduced during the crystallization, oxidoreduction of 5α-DHT occurred. The locations of A-dione and epi-ADT were identified in the steroid-binding sites of two 3α-HSD3 molecules per crystal asymmetric unit. An overlay showed that A-dione and epi-ADT were oriented upside-down and flipped relative to each other, providing structural clues for 5α-DHT reverse binding in the enzyme with the generation of different products. Moreover, we report the crystal structure of the 3α-HSD3·NADP+·4-dione (4-androstene-3,17-dione) complex. When a specific siRNA (100 nM) was used to suppress 3α-HSD3 expression without interfering with 3α-HSD4, which shares a highly homologous active site, the 5α-DHT concentration increased, whereas MCF7 cell growth was suppressed. The present study provides structural clues for 5α-DHT reverse binding within 3α-HSD3, and demonstrates for the first time that down-regulation of 3α-HSD3 decreases MCF7 breast cancer cell growth.


2020 ◽  
Vol 43 (12) ◽  
pp. 1711-1716
Author(s):  
M. F. Faienza ◽  
F. Baldinotti ◽  
G. Marrocco ◽  
N. TyuTyusheva ◽  
D. Peroni ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document