更新于：2024-11-21

Clostebol Acetate

醋酸氯司替勃

更新于：2024-11-21

概要

概要

基本信息

药物类型

小分子化药

别名

4-Chlorotestosterone acetate、Chlorotestosterone acetate、醋酸4-氯睾丸素

+ [1]

靶点

作用机制

AR激动剂(雄激素受体激动剂)

治疗领域

内分泌与代谢疾病血液及淋巴系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

雄激素缺乏症白细胞减少骨质疏松症+ [1]

非在研适应症-

原研机构-

在研机构-

非在研机构-

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)批准上市

特殊审评-

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结构

分子式C21H29ClO3

InChIKeyXYGMEFJSKQEBTO-KUJXMBTLSA-N

CAS号855-19-6

关联

100 项与醋酸氯司替勃相关的临床结果

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100 项与醋酸氯司替勃相关的转化医学

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100 项与醋酸氯司替勃相关的专利（医药）

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148

项与醋酸氯司替勃相关的文献（医药）

2024-03-01·The Journal of Steroid Biochemistry and Molecular Biology

Biotransformation of anabolic androgenic steroids in human skin cells

Article

作者: Karim, Ziaul ; Zoschke, Christian ; Parr, Maria Kristina ; de la Torre, Xavier ; Schlörer, Nils ; Botrè, Francesco ; Liu, Lingyu

In comparison to well-known drug-metabolizing organs such as the liver, the metabolic capacity of human skin is still not well elucidated despite the widespread use of topical drug application. To gain a comprehensive insight into anabolic steroid metabolism in the skin, six structurally related anabolic androgenic steroids, testosterone, metandienone, methyltestosterone, clostebol, dehydrochloromethyltestosterone, and methylclostebol, were applied to human keratinocytes and fibroblasts derived from the juvenile foreskin. Phase I metabolites obtained from incubation media were analyzed by gas chromatography-mass spectrometry. The 5α-reductase activity was predominant in the metabolic pathways as supported by the detection of 5α-reduced metabolites after incubation of testosterone, methyltestosterone, clostebol, and methylclostebol. Additionally, the stereochemistry structures of fully reduced metabolites (4α,5α-isomers) of clostebol and methylclostebol were newly confirmed in this study by the help of inhouse synthesized reference materials. The results provide insights into the steroid metabolism in human skin cells with respect to the characteristics of the chemical structures.

2023-09-28·Archives of microbiology

Gut microbiome of Crocodylus porosus and cellular stress: inhibition of nitric oxide, interleukin 1-beta, tumor necrosis factor-alpha, and prostaglandin E2 in cerebrovascular endothelial cells.

Article

作者: Alharbi, Ahmad M ; Siddiqui, Ruqaiyyah ; Alfahemi, Hasan ; Khan, Naveed Ahmed ; Akbar, Noor ; Maciver, Sutherland K

Crocodiles are renowned for their resilience and capacity to withstand environmental stressors, likely influenced by their unique gut microbiome. In this study, we determined whether selected gut bacteria of Crocodylus porosus exhibit anti-inflammatory effects in response to stress, by measuring nitric oxide release, interleukin 1-beta, tumor necrosis factor-alpha, and prostaglandin E2 in cerebrovascular endothelial cells. Using the Griess assay, the findings revealed that among several C. porosus gut bacterial isolates, the conditioned media containing the metabolites of two bacterial strains (CP27 and CP36) inhibited nitric oxide production significantly, in response to the positive control, i.e., taxol-treatment. Notably, CP27 and CP36 were more potent at reducing nitric oxide production than senloytic compounds (fisetin, quercetin). Using enzyme linked immunosorbent assays, the production of pro-inflammatory cytokines (IL-1β, TNF-α, PGE2), was markedly reduced by treatment with CP27 and CP36, in response to stress. Both CP27 and CP36 contain a plethora of metabolites to exact their effects [(3,4-dihydroxyphenylglycol, 5-methoxytryptophan, nifedipine, 4-chlorotestosterone-17-acetate, 3-phenoxypropionic acid, lactic acid, f-Honaucin A, l,l-Cyclo(leucylprolyl), 3-hydroxy-decanoic acid etc.], indicative of their potential in providing protection against cellular stress. Further high-throughput bioassay-guided testing of gut microbial metabolites from crocodiles, individually as well as in combination, together with the underlying molecular mechanisms, in vitro and in vivo will elucidate their value in the rational development of innovative therapies against cellular stress/gut dysbiosis.

2023-08-01·Toxicology Letters

Assessment of the inhibitory potential of anabolic steroids towards human AKR1D1 by computational methods and in vitro evaluation

Article

作者: Kędzierski, Jacek ; Allard, Julien A ; Smieško, Martin ; Odermatt, Alex

Exposure to xenobiotics can adversely affect biochemical reactions, including hepatic bile acid synthesis. Bile acids are essential for dissolving lipophilic compounds in the hydrophilic environment of the gastrointestinal tract. The critical micellar concentration of bile acids depends on the Δ4-reduction stereochemistry, with the 3-oxo-5β-steroid-Δ4-dehydrogenase (AKR1D1) introducing the cis ring A/B conformation. Loss-of-function mutations in AKR1D1 cause hepatic cholestasis, which, if left untreated can progress into steatosis and liver cirrhosis. Furthermore, AKR1D1 is involved in clearing steroids with an A-ring Δ4-double bond. Here, we tested whether anabolic-androgenic steroids (AAS), often taken off-label at high doses, might inhibit AKR1D1, thereby potentially causing hepatotoxicity. A computational molecular model was established and used for virtual screening of the DrugBank database consisting of 2740 molecules, yielding mainly steroidal hits. Fourteen AAS were selected for in vitro evaluation, as such compounds can reach high hepatic concentrations in an abuse situation. Nandrolone, clostebol, methasterone, drostanolone, and methenolone inhibited to various extent the AKR1D1-mediated reduction of testosterone. Molecular modeling suggests that 9 out of 14 investigated AAS are competitive inhibitors. Moreover quantum mechanical calculations show that nadrolone and clostebol are substrates of AKR1D1 with different activation energy barriers for the hydrogen transfer from cofactor to the C5 position affecting their turnover. In this multidisciplinary approach, we established a molecular model of AKR1D1, identified several AAS as inhibitors, and described their binding mode. This approach may be applied to study other classes of inhibitors including non-steroidal compounds.

100 项与醋酸氯司替勃相关的药物交易

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