114011-35-7Relevant articles and documents
Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle
Dansey, Mara V.,Alvarez, Lautaro D.,Samaja, Gisela,Escudero, Daiana S.,Veleiro, Adriana S.,Pecci, Adal,Castro, Olga A.,Burton, Gerardo
, p. 175 - 184 (2015)
Dafachronic acids (DAs) are 3-keto cholestenoic acids bearing a carboxylic acid moiety at the end of the steroid side chain. These compounds interact with the DAF-12 receptor, a ligand-dependent transcription factor that acts as a molecular switch mediating the choice between arrest at diapause or progression to reproductive development and adult lifespan in different nematodes. Recently, we reported that the 27-nor-Δ4-DA was able to directly activate DAF-12 in a transactivation cell-based luciferase assay and rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants. In the present paper, to investigate further the relationship between the structure of the steroid side chain and DAF-12 activity, we evaluated the in vitro and in vivo activity of Δ4-DA analogues with modified side chains using transactivation cell-based assays and daf-9(dh6) C. elegans mutants. Our results revealed that introduction of a 24,25-double bond on the cholestenoic acid side chain did not affect DAF-12 activity, whereas shortening the side chain lowered the activity. Most interestingly, the C24 alcohol 24-hydroxy-4-cholen-3-one (6) was an antagonist of the DAF-12 receptor both in vitro and in vivo.
Design and synthesis of a crosslinker for studying intracellular steroid trafficking pathways
Byrd, Katherine M.,Arieno, Marcus D.,Kennelly, Megan E.,Estiu, Guillermina,Wiest, Olaf,Helquist, Paul
, p. 3843 - 3851 (2015)
A crosslinker was designed and synthesized as a molecular tool for potential use in probing the intracellular trafficking pathways of steroids. The design was guided by computational modeling based upon a model for the transfer of cholesterol between two
Smooth receptor ligand
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Paragraph 0085; 0140; 0142-0143; 0151, (2020/04/01)
The invention relates to the technical field of biology, particularly to a smooth receptor ligand, and provides a smooth receptor ligand or an isomer prodrug, a solvate and a pharmaceutically acceptable salt thereof, wherein the structural formula of the smooth receptor ligand is A-linker-B, A is an extracellular domain ligand structure, B is a transmembrane domain ligand structure, and Linker isa linear subunit inactive to the smooth receptor. According to the novel double-end small molecule ligand for the smooth receptor, by combining the crystal structure data of the smooth receptor, a linker is introduced into the proper sites of an extracellular domain ligand and a transmembrane domain ligand to obtain brand-new double-end ligand small molecules, so that the interaction between the ligand and the receptor and the biological activity of the ligand are enhanced.
