更新于：2024-11-01

SRD5A1 x SRD5A2

更新于：2024-11-01

基本信息

关联

项与 SRD5A1 x SRD5A2 相关的药物

XNA-2

靶点

SRD5A1 x SRD5A2

作用机制

SRD5A1抑制剂 [+1]

在研机构-

原研机构

Xenna Corp.

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SRD5A1 x SRD5A2 相关的临床结果

登录后查看更多信息

100 项与 SRD5A1 x SRD5A2 相关的转化医学

登录后查看更多信息

0 项与 SRD5A1 x SRD5A2 相关的专利（医药）

登录后查看更多信息

112

项与 SRD5A1 x SRD5A2 相关的文献（医药）

2024-07-01·The Journal of Steroid Biochemistry and Molecular Biology

5α-reduction of epitestosterone is catalysed by human SRD5A1 and SRD5A2 and increases androgen receptor transactivation

Article

作者: Schiffer, Lina ; Arlt, Wiebke ; Storbeck, Karl-Heinz

Epitestosterone is a stereoisomer of the active androgen testosterone and its circulating concentrations are similar to those of testosterone in women and children. However, its biological function and pathways of metabolism remain unknown. The structural similarity to testosterone suggests a potential function in the modulation of androgen receptor signalling. It is well established that the conversion of testosterone to 5α-dihydrotestosterone enhances local androgen receptor signalling. In this study, we show that epitestosterone is metabolized to 5α-dihydroepitestosterone by both human steroid 5α-reductase isoforms, SRD5A1 and SRD5A2. Using two different variations of a reporter assay for transactivation of the human androgen receptor, we show that epitestosterone is a partial AR agonist and that the 5α-reduction of epitestosterone increases its androgenic activity. In line with this, we show that 5α-reduction of epitestosterone reduces its ability to antagonize 5α-dihydrotestosterone-induced androgen receptor transactivation. In conclusion, we provide evidence that steroid 5α-reductases regulate the modulatory effect of epitestosterone on androgen receptor signalling.

2023-12-01·Biomedicine & Pharmacotherapy

A common germline variant in CYP11B1 is associated with adverse clinical outcome of treatment with abiraterone or enzalutamide

Article

作者: Koolen, Stijn L W ; de Jonge, Evert ; de Wit, Ronald ; Bergman, Andries M ; Meertens, Marinda ; Buck, Stefan A J ; Oomen-de Hoop, Esther ; Coenen, Marieke J H ; Mathijssen, Ron H J ; van Schaik, Ron H N ; Huitema, Alwin D R ; van Ooijen, Frederiek M F

Extragonadal androgens play a pivotal role in prostate cancer disease progression on androgen receptor signaling inhibitors (ARSi), including abiraterone and enzalutamide. We aimed to investigate if germline variants in genes involved in extragonadal androgen synthesis contribute to resistance to ARSi and may predict clinical outcomes on ARSi. We included ARSi naive metastatic prostate cancer patients treated with abiraterone or enzalutamide and determined 18 germline variants in six genes involved in extragonadal androgen synthesis. Variants were tested in univariate and multivariable analysis for the relation with overall survival (OS) and time to progression (TTP) by Cox regression, and PSA response by logistic regression. A total of 275 patients were included. From the investigated genes CYP17A1, HSD3B1, CYP11B1, AKR1C3, SRD5A1 and SRD5A2, only rs4736349 in CYP11B1 in homozygous form (TT), present in 54 patients (20%), was related with a significantly worse OS (HR = 1.71, 95% CI 1.09 - 2.68, p = 0.019) and TTP (HR = 1.50, 95% CI 1.08 - 2.09, p = 0.016), and was related with a significantly less frequent PSA response (OR = 0.48, 95% CI 0.24 - 0.96, p = 0.038) on abiraterone or enzalutamide in a multivariable analysis. The frequent germline variant rs4736349 in CYP11B1 is, as homozygote, an independent negative prognostic factor for treatment with abiraterone or enzalutamide in ARSi naive metastatic prostate cancer patients. Our findings warrant prospective investigation of this potentially important predictive biomarker.

2023-03-01·Cancer Prevention Research

Chemopreventive Effect of Cinnamon and Its Bioactive Compounds in a Rat Model of Premalignant Prostate Carcinogenesis

Article

作者: Gogulothu, Ramesh ; Mir, Irfan Ahmad ; Gopalakrishnan, Srividya ; Ismail, Ayesha ; Dhaware, Mahamaya ; Siginam, Siva Ramakrishna ; Sudharma, Athira Anilkumar ; Mullapudi, Surekha Venkata

AbstractCinnamon and its bioactive compounds inhibit prostate cancer cell proliferation in vitro. The aim of the current study was to assess the chemopreventive efficacy of cinnamon (CN) and its bioactive compounds in vivo using N-methyl-N-nitrosourea (MNU) and testosterone (T) to induce prostate carcinogenesis in male Wistar/National Institute of Nutrition rats. Cancer-induced (CI) rats (n = 10) developed prostatic hyperplasia and prostatic intraepithelial neoplasia. These histopathologic changes were diminished in CI rats fed for 4 months with diets supplemented with either CN (n = 20) or its bioactive compounds (cinnamaldehyde, n = 10 and procyanidin B2, n = 10). Androgen receptor (AR) expression was lower in the prostates of CI rats than in control, but the AR target gene, probasin, was robustly upregulated. Treatment of CI rats with CN or its bioactive compounds upregulated AR expression but inhibited the expression of the 5-alpha reductase genes (Srd5a1 and Srd5a2) and did not further increase probasin expression, suggesting blunted transcriptional activity of AR due to the limited availability of dihydrotestosterone. MNU+T induced an altered oxidant status in rat prostate, which was reflected by an increase in lipid peroxidation and DNA oxidation. These changes were completely or partially corrected by treatment with CN or the bioactive compounds. CN and its active components increased the activity of the apoptotic enzymes caspase-8 and caspase-3 in the prostates of CI rats. In conclusion, our data demonstrate that CN and its bioactive compounds have inhibitory effects on premalignant prostate lesions induced by MNU + T and, therefore, may be considered for the chemoprevention of prostate cancer.Prevention Relevance:The research work presented in this article demonstrates the chemopreventive efficacy of CN and its bioactive compounds in a rat model of premalignant prostate cancer.