Modeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics.

• Tác giả: Karar Alwaeli, Michael T Applegate, Jaskaran Bhogal, Christine Chhun, Tracie L Feldman, Aleksandra Grozic, Jennifer F Hackney, Samir Ibrahim, Peter W Jurutka, Ichiro Kaneko, Zainab Khan, Ning Ma, Mairi MacNeill, Pamela A Marshall, Natalia Nguyen, Kayla J Pomeroy, San Raban, Joseph T Sarnowski, Michael A Sausedo, Pritika H Shahani, Johnathon Swierski, Arjan van der Vaart, Carl E Wagner, Michael R Wentzel, Joseph W Ziller
• Ngôn ngữ: eng
• Ký hiệu phân loại: 912.01 Philosophy and theory
• Thông tin xuất bản: England : Bioorganic & medicinal chemistry , 2025
• Bộ sưu tập: NCBI
• ID: 60574

Tóm tắt

Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay. The EC