Last update 01 Nov 2024

SRD5A3

Last update 01 Nov 2024

Basic Info

Synonyms

3-oxo-5-alpha-steroid 4-dehydrogenase 3, FLJ13352, Polyprenol reductase

+ [8]

Introduction

Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol (PubMed:20637498). Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation (PubMed:20637498). Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism (PubMed:20637498). Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT) (PubMed:17986282, PubMed:26855069).

Drugs associated with SRD5A3

DG01

Target

GSPT1 x SRD5A3

Mechanism

GSPT1 degraders [+1]

Active Org.

Suzhou Degen Biomedical Co., Ltd.

Originator Org.

Suzhou Degen Biomedical Co., Ltd.

Active Indication

Castration-Resistant Prostatic Cancer [+2]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SRD5A3

CTR20243467 / Not yet recruitingPhase 1

评价 DG01 在前列腺癌患者中的安全性、耐受性、药物代谢动力学特征和初步有效性的Ⅰ 期临床研究

[Translation] Phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of DG01 in patients with prostate cancer

主要研究目的： 1、评估DG01的安全性、耐受性和最大耐受剂量（MTD）及临床II期推荐剂量（RP2D）； 2、评估DG01在前列腺癌患者中的药代动力学特征。次要研究目的： 1、评估DG01在前列腺癌患者中的初步有效性。探索性目的： 1、探索DG01在前列腺癌患者中抗肿瘤疗效相关生物标志物的表达。

[Translation]

Main research objectives: 1. Evaluate the safety, tolerability and maximum tolerated dose (MTD) of DG01 and the recommended dose (RP2D) for phase II clinical trials; 2. Evaluate the pharmacokinetic characteristics of DG01 in patients with prostate cancer. Secondary research objectives: 1. Evaluate the preliminary efficacy of DG01 in patients with prostate cancer. Exploratory objectives: 1. Explore the expression of biomarkers related to the anti-tumor efficacy of DG01 in patients with prostate cancer.

Start Date-

Sponsor / Collaborator

Suzhou Degen Biomedical Co., Ltd.

100 Clinical Results associated with SRD5A3

100 Translational Medicine associated with SRD5A3

0 Patents (Medical) associated with SRD5A3

199

Literatures (Medical) associated with SRD5A3

31 Dec 2024·Annals of Medicine

Analysis of the implication of steroid 5 alpha-reductase 3 on prognosis and immune microenvironment in Liver Hepatocellular Carcinoma

Article

Author: Liu, Ziwei ; Lin, Weida ; Lu, Yuming ; Liu, Xuesong ; Liu, XiaoQin ; Zheng, Yu ; Mao, Kai ; Chen, Nanguan

INTRODUCTIONThis study combined the bioinformatics and in vitro experiment-related technologies to analyze the impact of steroid 5 alpha-reductase 3 (SRD5A3) on the prognosis and immune microenvironment of Liver Hepatocellular Carcinoma (LIHC).METHODGene expression and clinical data were obtained from public databases. The prognosis was evaluated using survival, multifactor Cox, enrichment, and mutation analyses. This was then verified through in vitro experiments.RESULTSThe expression level of SRD5A3 in LIHC tissues was significantly higher than that in the adjacent tissues. Kaplan-Meier survival analysis showed that high SRD5A3 expression was associated with poor overall survival (OS) and short progression-free survival in patients with LIHC. Multivariate Cox regression analysis revealed that positive SRD5A3 expression was an independent risk factor for OS in patients with LIHC. Expression of SRD5A3 was negatively correlated with immune cell infiltration of CD4+ T, CD8+ T, and B cells. GO and KEGG enrichment analyses showed that SRD5A3 was significantly enriched in signaling- and tumor metastasis-related pathways. Nomogram and calibration curve showed that the predicted performance of the model was consistent with the actual results. In vitro results confirmed that SRD5A3 knockdown inhibited the migration, invasion, and proliferation of LIHC cells.CONCLUSIONSSRD5A3 is actively expressed in LIHC, and positive expression of SRD5A3 is an independent risk factor for different prognoses in patients with LIHC. SRD5A3 can promote the proliferation, migration, and invasion of liver cancer cells and is related to short immune infiltration in patients with LIHC.

01 Dec 2024·Mammalian Genome

Comprehensive analysis of chromosomal breakpoints and candidate genes associated with male infertility: insights from cytogenetic studies and expression analyses

Article

Author: Kakavand, Kianoush ; Sabbaghian, Marjan ; Hassanzadeh, Vahideh ; Masoudi, Najmeh Sadat ; Meybodi, Anahita Mohseni ; Moradi, Shabnam Zarei ; Shahhoseini, Maryam ; Zamanian, Mohammadreza ; Hossein Garakani, Melika ; Ghaheri, Azadeh

The study aimed to investigate prevalent chromosomal breakpoints identified in balanced structural chromosomal anomalies and to pinpoint potential candidate genes linked with male infertility. This was acchieved through a comprehensive approach combining RNA-seq and microarray data analysis, enabling precise identification of candidate genes. The Cytogenetics data from 2,500 infertile males referred to Royan Research Institute between 2009 and 2022 were analyzed, with 391 cases meeting the inclusion criteria of balanced chromosomal rearrangement. Of these, 193 cases exhibited normal variations and were excluded from the analysis. By examining the breakpoints, potential candidate genes were suggested. Among the remaining 198 cases, reciprocal translocations were the most frequent anomaly (129 cases), followed by Robertsonian translocations (43 cases), inversions (34 cases), and insertions (3 cases).Some patients had more than one chromosomal abnormality. Chromosomal anomalies were most frequently observed in chromosomes 13 (21.1%), 14 (20.1%), and 1 (16.3%) with 13q12, 14q12, and 1p36.3 being the most prevalent breakpoints, respectively. Chromosome 1 contributed the most to reciprocal translocations (20.2%) and inversions (17.6%), while chromosome 14 was the most involved in the Robertsonian translocations (82.2%). The findings suggested that breakpoints at 1p36.3 and 14q12 might be associated with pregestational infertility, whereas breakpoints at 13q12 could be linked to both gestational and pregestational infertility. Several candidate genes located on common breakpoints were proposed as potentially involved in male infertility. Bioinformatics analyses utilizing three databases were conducted to examine the expression patterns of 78 candidate genes implicated in various causes of infertility.‏ In azoospermic individuals, significant differential expression was observed in 19 genes: 15 were downregulated (TSSK2, SPINK2, TSSK4, CDY1, CFAP70, BPY2, BTG4, FKBP6, PPP2R1B, SPECC1L, CENPJ, ‏SKA3, FGF9, NODAL, CLOCK), while four genes were upregulated ‏(‏HSPB1, MIF, PRF1, ENTPD6). In the case of Asthenozoospermia, seven genes showed significant upregulation (PRF1, DDX21, KIT, SRD5A3, MTCH1, DDX50, NODAL). Though RNA-seq data for Teratozoospermia were unavailable, microarray data revealed differential expression insix genes: three downregulated (BUB1, KLK4, PIWIL2) and three upregulated (AURKC, NPM2, RANBP2). These findings enhance our understanding of the molecular basis of male infertility and could provide valuable insights for future diagnostic and therapeutic strategies.

01 Dec 2024·Poultry Science

Novel insights into the circadian modulation of lipid metabolism in chicken livers revealed by RNA sequencing and weighted gene co-expression network analysis

Article

Author: Chen, Jilan ; Xiong, Hui ; Li, Xiangchen ; Song, Dan ; Sun, Yanyan ; Wang, Panlin ; Wu, Yongshu ; Du, Xue ; Li, Yunlei ; Li, Fang ; Liu, Lu ; Xie, Xiuyu

The circadian clock is crucial for maintaining lipid metabolism homeostasis in mammals. Despite the economic importance of fat content in poultry, research on the regulatory effects and molecular mechanisms of the circadian clock on avian hepatic lipid metabolism has been limited. In this study, we observed significant diurnal variations (P<0.05) in triglyceride (TG), free fatty acids (FFA), fatty acid synthase (FAS), and total cholesterol (TC) levels in the chicken embryonic liver under 12-h light/12-h dark incubation conditions, with TG, FFA, and TC concentrations showing significant cosine rhythmic oscillations (P<0.05). However, such rhythmic variations were not observed under complete darkness incubation conditions. Using transcriptome sequencing technology, we identified 157 genes significantly upregulated at night and 313 genes significantly upregulated during the 12-h light/12-h dark cycle. These circadian differential genes are involved in processes and pathways such as lipid catabolic process regulation, meiotic cell cycle, circadian rhythm regulation, positive regulation of the MAPK cascade, and glycerolipid metabolism. Weighted gene co-expression network analysis (WGCNA) revealed 3 modules-green, blue, and red-that significantly correlate with FFA, FAS, and TG, respectively. Genes within these modules were enriched in processes and pathways including the cell cycle, light stimulus response, circadian rhythm regulation, phosphorylation, positive regulation of the MAPK cascade, and lipid biosynthesis. Notably, we identified ten hub genes, including protein kinase C delta (PRKCD), polo like kinase 4 (PLK4), clock circadian regulator (CLOCK), steroid 5 alpha-reductase 3 (SRD5A3), BUB1 mitotic checkpoint serine/threonine kinase (BUB1B), shugoshin 1 (SGO1), NDC80 kinetochore complex component (NDC80), NIMA related kinase 2 (NEK2), minichromosome maintenance complex component 4 (MCM4), polo like kinase 1 (PLK1), potentially link circadian regulation with lipid metabolic homeostasis. These findings demonstrate the regulatory role of the circadian clock in chicken liver lipid metabolism homeostasis and provide a theoretical basis and molecular targets for optimizing the circadian clock to reduce excessive fat deposition in chickens, which is significant for the healthy development of the poultry industry.

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