2007
DOI: 10.1124/mol.107.038208
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Challenges and Opportunities of Trapping Ligands

Abstract: Because gonadotropin-releasing hormone (GnRH) analogs constitute an important class of therapeutics for various reproductive and hormone-dependent disorders, many novel compounds have been discovered and studied. Several orally active nonpeptide GnRH antagonists have recently gained increased attention. In the study published in this issue of Molecular Pharmacology, Kohout et al. (p. 238) used smallmolecule TAK-013 (sufugolix; developed previously by Takeda Chemical Industries) as a tool to elucidate the mech… Show more

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Cited by 6 publications
(4 citation statements)
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“…CBR003PS, a parenteral cephalosporin, was initially developed to selectively target Gram-positive bacteria's cell walls, which can explain the lack of toxicity in mammalian cells [27]. On the other hand, CBR013PS has shown a favorable safety profile in vitro and in vivo, which may also explain the lack of toxicity in our cell-based assays [28]. The favorable safety profile is an important point since it has been documented that conventional HIV protease inhibitors are associated with adverse side effects, especially after prolonged use.…”
Section: Discussionmentioning
confidence: 99%
“…CBR003PS, a parenteral cephalosporin, was initially developed to selectively target Gram-positive bacteria's cell walls, which can explain the lack of toxicity in mammalian cells [27]. On the other hand, CBR013PS has shown a favorable safety profile in vitro and in vivo, which may also explain the lack of toxicity in our cell-based assays [28]. The favorable safety profile is an important point since it has been documented that conventional HIV protease inhibitors are associated with adverse side effects, especially after prolonged use.…”
Section: Discussionmentioning
confidence: 99%
“…However, there is also pharmacologically justified possibility that super-agonists are in general less capable of inducing multiple conformations and therefore much less biased ( 65 ). Selected super-agonists are known to have an extended receptor-residence time, which in turn may affect GPHR interactions with the cell adapter proteins, endosome signaling, and signal compartmentalization ( 61 , 66 68 ).…”
Section: Gph Super-agonists – Tools In Structure–function Studiesmentioning
confidence: 99%
“…Synthetic quinazolinones are also noted for their diverse biological activities extensively reported and summarized in review articles. [7,8,26.27] The thienopyrimidinone system is noteworthy as a core structure of Relugolix [28] and Sufugolix, [29,30] the therapeutics for the treatment of prostate cancer, endometriosis, and uterine fibroids, as well as a number of antiproliferative, [31] antitumor, [32] and cytotoxic agents. [33] The pyrrolo [2,3-d]pyrimidin-4-one framework is contained in the structure of the natural nucleoside antibiotic Cadeguomycin, [34] the anticancer drug Pemetrexed, [35] antiparasitic agents, [36] folic acid antagonists, [37,38] cytokine modulators.…”
Section: Introductionmentioning
confidence: 99%