scholarly journals Modeling, Synthesis, and Biological Evaluation of Potential Retinoid X Receptor (RXR) Selective Agonists: Novel Analogues of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic Acid (CD3254)

2013 ◽  
Vol 56 (21) ◽  
pp. 8432-8454 ◽  
Author(s):  
Peter W. Jurutka ◽  
Ichiro Kaneko ◽  
Joanna Yang ◽  
Jaskaran S. Bhogal ◽  
Johnathon C. Swierski ◽  
...  
Keyword(s):  
Acrylic Acid ◽  
Benzoic Acid ◽  
Biological Evaluation ◽  
Retinoid X Receptor ◽  
Selective Agonists ◽  
Synthesis And Biological Evaluation

scholarly journals Modeling, Synthesis and Biological Evaluation of Potential Retinoid-X-Receptor (RXR) Selective Agonists: Analogs of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahyro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and 6-(Ethyl(4-isobutoxy-3-isopropylphenyl)amino)nicotinic Acid (NEt-4IB)

2021 ◽  
Vol 22 (22) ◽  
pp. 12371
Author(s):  
Peter W. Jurutka ◽  
Orsola di Martino ◽  
Sabeeha Reshi ◽  
Sanchita Mallick ◽  
Zhela L. Sabir ◽  
...  
Keyword(s):  
Benzoic Acid ◽  
Nicotinic Acid ◽  
Leukemia Cell ◽  
Biological Evaluation ◽  
Retinoid X Receptor ◽  
Proliferative Potential ◽  
The Novel ◽  
Leukemia Cell Lines ◽  
Ic50 Values ◽  
Synthesis And Biological Evaluation

Five novel analogs of 6-(ethyl)(4-isobutoxy-3-isopropylphenyl)amino)nicotinic acid—or NEt-4IB—in addition to seven novel analogs of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), a FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Bexarotene treatment elicits side-effects by provoking or disrupting other RXR-dependent pathways. Analogs were assessed by the modeling of binding to RXR and then evaluated in a human cell-based RXR-RXR mammalian-2-hybrid (M2H) system as well as a RXRE-controlled transcriptional system. The analogs were also tested in KMT2A-MLLT3 leukemia cells and the EC50 and IC50 values were determined for these compounds. Moreover, the analogs were assessed for activation of LXR in an LXRE system as drivers of ApoE expression and subsequent use as potential therapeutics in neurodegenerative disorders, and the results revealed that these compounds exerted a range of differential LXR-RXR activation and selectivity. Furthermore, several of the novel analogs in this study exhibited reduced RARE cross-signaling, implying RXR selectivity. These results demonstrate that modification of partial agonists such as NEt-4IB and potent rexinoids such as bexarotene can lead to compounds with improved RXR selectivity, decreased cross-signaling of other RXR-dependent nuclear receptors, increased LXRE-heterodimer selectivity, and enhanced anti-proliferative potential in leukemia cell lines compared to therapeutics such as 1.

ChemInform Abstract: Substituted Hexahydrobenzo(f)thieno(c)quinolines as Dopamine D1- Selective Agonists: Synthesis and Biological Evaluation in vitro and in vivo.

ChemInform ◽  
2010 ◽  
Vol 28 (39) ◽  
pp. no-no
Author(s):  
M. R. MICHAELIDES ◽  
Y. HONG ◽  
S. JUN. DIDOMENICO ◽  
E. K. BAYBURT ◽  
K. E. ASIN ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Selective Agonists ◽  
Synthesis And Biological Evaluation
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