“…As for the first direction, the efforts were mainly dedicated to the chemical modifications of bicalutamide, enzalutamide, and reported bioactive compounds including natural products. [72][73][74][75][76][77][78] ARN-509 (6, apalutamide) may be the most representative example, and it was synthesized as a derivative of enzalutamide based on structure-activity relationship (SAR)-guided medicinal chemistry. ARN-509 cannot restrain nuclear localization and DNA binding of AR, but bind to the AR LBP (IC 50 = 16 nM) with a 10-fold affinity than bicalutamide (median IC 50 = 160 nM), and the dosage of 30 mg/kg/d showed the same efficacy as 100 mg/kg/d of enzalutamide in a xenograft model of human CRPC.…”
Section: Ar Antagonists Targeting Lbp Of Lbdmentioning
confidence: 99%
“…In general, the studies about the discovery and development of LBD‐targeting antagonists have two directions: (1) discovery of more potent derivatives of marketed drugs and bioactive compounds; (2) exploration of novel scaffold antagonists by high throughput screening (HTS) based on cell models or the combination strategy involving virtual screening (VS) and experimental bioassays. As for the first direction, the efforts were mainly dedicated to the chemical modifications of bicalutamide, enzalutamide, and reported bioactive compounds including natural products . ARN‐509 ( 6 , apalutamide) may be the most representative example, and it was synthesized as a derivative of enzalutamide based on structure‐activity relationship (SAR)‐guided medicinal chemistry.…”
Androgen receptor (AR) is closely associated with a group of hormone‐related diseases including the cancers of prostate, breast, ovary, pancreas, etc and anabolic deficiencies such as muscle atrophy and osteoporosis. Depending on the specific type and stage of the diseases, AR ligands including not only antagonists but also agonists and modulators are considered as potential therapeutics, which makes AR an extremely interesting drug target. Here, we at first review the current understandings on the structural characteristics of AR, and then address why and how AR is investigated as a drug target for the relevant diseases and summarize the representative antagonists and agonists targeting five prospective small molecule binding sites at AR, including ligand‐binding pocket, activation function‐2 site, binding function‐3 site, DNA‐binding domain, and N‐terminal domain, providing recent insights from a target and drug development view. Further comprehensive studies on AR and AR ligands would bring fruitful information and push the therapy of AR relevant diseases forward.
“…As for the first direction, the efforts were mainly dedicated to the chemical modifications of bicalutamide, enzalutamide, and reported bioactive compounds including natural products. [72][73][74][75][76][77][78] ARN-509 (6, apalutamide) may be the most representative example, and it was synthesized as a derivative of enzalutamide based on structure-activity relationship (SAR)-guided medicinal chemistry. ARN-509 cannot restrain nuclear localization and DNA binding of AR, but bind to the AR LBP (IC 50 = 16 nM) with a 10-fold affinity than bicalutamide (median IC 50 = 160 nM), and the dosage of 30 mg/kg/d showed the same efficacy as 100 mg/kg/d of enzalutamide in a xenograft model of human CRPC.…”
Section: Ar Antagonists Targeting Lbp Of Lbdmentioning
confidence: 99%
“…In general, the studies about the discovery and development of LBD‐targeting antagonists have two directions: (1) discovery of more potent derivatives of marketed drugs and bioactive compounds; (2) exploration of novel scaffold antagonists by high throughput screening (HTS) based on cell models or the combination strategy involving virtual screening (VS) and experimental bioassays. As for the first direction, the efforts were mainly dedicated to the chemical modifications of bicalutamide, enzalutamide, and reported bioactive compounds including natural products . ARN‐509 ( 6 , apalutamide) may be the most representative example, and it was synthesized as a derivative of enzalutamide based on structure‐activity relationship (SAR)‐guided medicinal chemistry.…”
Androgen receptor (AR) is closely associated with a group of hormone‐related diseases including the cancers of prostate, breast, ovary, pancreas, etc and anabolic deficiencies such as muscle atrophy and osteoporosis. Depending on the specific type and stage of the diseases, AR ligands including not only antagonists but also agonists and modulators are considered as potential therapeutics, which makes AR an extremely interesting drug target. Here, we at first review the current understandings on the structural characteristics of AR, and then address why and how AR is investigated as a drug target for the relevant diseases and summarize the representative antagonists and agonists targeting five prospective small molecule binding sites at AR, including ligand‐binding pocket, activation function‐2 site, binding function‐3 site, DNA‐binding domain, and N‐terminal domain, providing recent insights from a target and drug development view. Further comprehensive studies on AR and AR ligands would bring fruitful information and push the therapy of AR relevant diseases forward.
“…The similar activity is demonstrated by derivatives possessing a carboxymethylene group at N‐3 position and arylidene or heteroarylmethylidene group at C‐5 position . Furthermore, derivatives of another five‐membered system, containing exocyclic sulfur atom, possess similar biological properties . These compounds are based on 2‐thioxo‐4‐imidazolidinone system and are called thiohydantoins.…”
Selected rhodanine‐3‐carboxylic acids derivatives were synthesized to determine the influence of the structure and the length of the linker between the carboxyl group and the nitrogen atom (N‐3) in the 2‐thioxo‐4‐thiazolidinone ring on their activity, monitored via interactions with human serum albumin. Based on fluorescence studies, we concluded that the length of the linker has a limited impact on these interactions. Additionally, we proposed the static mechanism of quenching for all the tested compounds. These derivatives seem to possess an anticancer activity in the nanomolar range with 3 as the most potent compound in both A2780 and A2780cisR cell lines.
Maca (Lepidium meyenii Walp.), a famous food supplement, has drawn an unprecedented international interest over the last two decades. It was assumed that glucosinolates, macamides, macaenes, and alkaloids are the main bioactive components of Maca before. Recently, a series of novel thiohydantoins which generally exhibit a variety of activities have been isolated from Maca. This review focuses on the progress on the main bioactive components of Maca and their biosynthetic pathway, which indicates that macamides, thiohydantoins, and some alkaloids may originate from glucosinolates. Interestingly, thiohydantoins from Maca are the first type of thiohydantoin derivatives to be found from a natural source and may contribute to some significant effects of Maca.Graphical Abstract
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