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Last update 08 May 2025

SRD5A3

Last update 08 May 2025

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 involved in the conversion of polyprenol into dolichol (PubMed:20637498, PubMed:38821050). Acts as a polyprenal reductase that mediates the reduction of polyprenal into dolichal in a NADP-dependent mechanism (PubMed:38821050). Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation (PubMed:20637498, PubMed:38821050). 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

/ 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 Date19 Nov 2024

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

123

Literatures (Medical) associated with SRD5A3

15 Apr 2025·The FASEB Journal

SPP1‐SRD5A3 signaling axis regulated lymph node metastasis by activating Mucin type O glycan biosynthesis

Article

Author: Song, Feifeng ; Zhang, Wanli ; Fu, Zhiyi ; Xu, Tong ; Gong, Shaobo ; Huang, Ping ; Zhang, Yiwen ; Jiang, Bo

AbstractLymph node metastasis (LNM) holds substantial implications for the recurrence and survival of cancer patients, but the intricate regulatory mechanisms underlying LNM remain poorly understood. MTOGB was dominantly increased in LNM of pan‐cancer, significantly activated in epithelial cells and enriched in LNM. Subsequently, we identified a specific epithelial cell subpopulation, EC4, located at the terminal of the LNM differentiation trajectory Lineage2. By intersecting differentially expressed genes in cluster 2, EC4 and Lineage2, we identified six crucial genes. Notably, the expression of Steroid 5α‐reductase 3 (SRD5A3) increased with the progression of LNM stages. Knockdown of SRD5A3 effectively suppressed the MTOGB, blocking metastasis in both cell and animal models. Nilotinib was screened as a candidate inhibitor of SRD5A3 and was confirmed to remarkably decrease cancer cell metastasis. SOX4 was identified as a potential transcription factor of SRD5A3, modulated by a dramatic increase in cell communication of SPP1+ macrophages in the immune microenvironment. The supernatant from SPP1+ macrophage significantly enhanced the expression of SOX4/SRD5A3 and the metastatic ability of cancer cells, and this effect was reversed by the deletion of SPP1. Collectively, our findings illuminate the SPP1‐SRD5A3 signaling as the crucial driver in LNM and suggest that its blockade could be a promising option for overcoming LNM.

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·Journal of Biological Chemistry

Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells

Article

Author: Contessa, Joseph N ; Caligiore, Francesco ; Matthijs, Gert ; Althoff, Charlotte R ; Kentache, Takfarinas ; Pieters, Eline ; Stanley, Pamela ; Souche, Erika ; Schulz, Céline ; Van Schaftingen, Emile ; Graff, Julie ; Foulquier, François ; Wilson, Matthew P ; Bommer, Guido T

Glycosylation-deficient Chinese hamster ovary cell lines have been instrumental in the discovery of N-glycosylation machinery. Yet, the molecular causes of the glycosylation defects in the Lec5 and Lec9 mutants have been elusive, even though for both cell lines a defect in dolichol formation from polyprenol was previously established. We recently found that dolichol synthesis from polyprenol occurs in three steps consisting of the conversion of polyprenol to polyprenal by DHRSX, the reduction of polyprenal to dolichal by SRD5A3, and the reduction of dolichal to dolichol, again by DHRSX. This led us to investigate defective dolichol synthesis in Lec5 and Lec9 cells. Both cell lines showed increased levels of polyprenol and its derivatives, concomitant with decreased levels of dolichol and derivatives, but no change in polyprenal levels, suggesting DHRSX deficiency. Accordingly, N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3. Furthermore, the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX were absent in membrane preparations derived from Lec5 and Lec9 cells, while the reduction of polyprenal to dolichal, catalyzed by SRD5A3, was unaffected. Long-read whole genome sequencing of Lec5 and Lec9 cells did not reveal mutations in the ORF of SRD5A3, but the genomic region containing DHRSX was absent. Lastly, we established the sequence of Chinese hamster DHRSX and validated that this protein has similar kinetic properties to the human enzyme. Our work therefore identifies the basis of the dolichol synthesis defect in Chinese hamster ovary Lec5 and Lec9 cells.

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SRD5A3

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