AKR1C3 Antibody (N_term) Blocking peptide
- Known as:
- AKR1C3 Antibody (N_term) Blocking short protein sequence
- Catalog number:
- BP10158a
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- AKR1C3 Antibody (N_term) Blocking peptide
Related genes to: AKR1C3 Antibody (N_term) Blocking peptide
- Gene:
- AKR1C3 NIH gene
- Name:
- aldo-keto reductase family 1 member C3
- Previous symbol:
- HSD17B5
- Synonyms:
- KIAA0119, DDX, HAKRB, PGFS
- Chromosome:
- 10p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-09-29
- Date modifiied:
- 2016-10-05
Related products to: AKR1C3 Antibody (N_term) Blocking peptide
Related articles to: AKR1C3 Antibody (N_term) Blocking peptide
- Castration-resistant prostate cancer (CRPC) is a lethal stage of prostate cancer (PC). This research sought to examine the functions and underlying mechanisms of N-methyladenosine (mA) methyltransferases in CRPC. Transcriptomic datasets from the Gene Expression Omnibus and The Cancer Genome Atlas were analyzed to identify dysregulated mA methyltransferases. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, wound healing, Transwell, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction, western blot, mA RNA immunoprecipitation quantitative PCR, co-immunoprecipitation, and mA quantification assays were performed to evaluate the phenotypic and molecular effects of methyltransferase-like 3 (METTL3). A xenograft tumor model was constructed by subcutaneous injection of lentivirus-transduced LNCaP cells into BALB/c nude mice. Hematoxylin and eosin staining was utilized to detect histopathological alterations, and immunohistochemistry was applied to measure Ki67 expression. METTL3 and methyltransferase-like 5 were upregulated, whereas methyltransferase-like 4 was downregulated. METTL3 knockdown suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition in LNCaP and C4-2 cells and suppressed xenograft tumor growth. METTL3 knockdown reduced dihydrotestosterone production and suppressed the protein expression of androgen receptor, kallikrein-related peptidase 3, and FK506 binding protein 5. METTL3 enhanced the mA methylation and transcript stability of aldo-keto reductase family 1 member C3 (AKR1C3). AKR1C3 overexpression notably reversed the anti-tumor effects induced by METTL3 knockdown. METTL3 acts as an epigenetic driver of CRPC by promoting AKR1C3 expression in an mA-dependent manner, highlighting the METTL3/AKR1C3 axis as a promising treatment target. - Source: PubMed
Nie QihongWu XiaoyuanHuang XinZeng MinYang ZhongshengLuo HailinDu Chuance - Aldo-keto reductase 1C3 (AKR1C3) is a key enzyme in androgen biosynthesis and a crucial driver of castration-resistant prostate cancer (CRPC), making it a promising therapeutic target. Unintended inhibition of its homologous isoforms AKR1C1 and AKR1C2 may cause off-target effects and is therefore highly undesirable. In this study, we rationally designed selective AKR1C3 inhibitors derived from the natural product osthole by optimizing the C8- and C7-substituents to target the SP1 and SP2 pockets, respectively, thereby achieving high selectivity for AKR1C3. Among the compounds synthesized, eleven exhibited potent inhibition of AKR1C3 (IC₅₀ < 0.1 μM) with high selectivity over AKR1C1. Notably, compounds 7k and 7o demonstrated significant antiproliferative activity in 22Rv1 cells (IC₅₀ = 3.05 μM and 5.45 μM, respectively). Crystallographic analysis revealed that the coumarin core anchors to the oxyanion site, while the C8-substitute interacts with the SP1 pocket, enhancing both potency and selectivity. In contrast to other coumarin-based inhibitors, osthole-derived compounds with extended C8-substitutions, interact with the SP1 pocket in a novel and distinct manner. These findings validate our design strategy of enhancing SP1 pocket binding to improve AKR1C3 selectivity over other AKR1C isoforms, and provide valuable structural insights for the further development of selective AKR1C3 inhibitors as potential therapeutics for CRPC. - Source: PubMed
Publication date: 2026/06/17
Zheng XuehuaHuang PingMi JingXiao YundanZheng LiWang HuilingLuo XiaociLiu RuoxuanZhang JianyeSun Mingna - Machine learning-guided virtual screening has the potential to accelerate early-stage drug discovery, but its practical utility is often limited by uncertain generalization to different chemical scaffolds and by insufficient prospective evaluation under realistic experimental constraints. To address these challenges, we conduct a target-driven virtual screening study using TAME-VS against aldo-keto reductase 1C3 (AKR1C3), an enzyme implicated in cancer progression and chemoresistance. By integrating automated target expansion, bioactivity data acquisition, and supervised learning, we construct classification models that leverage homolog-derived information to address data sparsity. Retrospective validation using inhibitor series absent from the training data demonstrates generalization to chemically different scaffolds beyond similarity-based prioritization. Prospective validation on newly designed derivatives shows that model-guided prioritization enriches active inhibitors relative to rational medicinal chemistry design alone under constrained synthesis capacity. S34-1035 and S34-1040 were further identified as potent and selective AKR1C3 inhibitors, and were shown to restore doxorubicin sensitivity in resistant breast cancer cells, establishing functional relevance. Building on these findings, a publicly accessible online server with a graphical user interface was further developed for the validated workflow of TAME-VS, enabling reproducible application by the broader community. - Source: PubMed
Publication date: 2026/06/15
Qiao LongjiangLi XinyuXing ShuaishuaiGuan QianwenNing KunHan WeijieZhang LuyuDai AnlanYang WeiqiLiu YinhangKwon Jason JGao XinSun HaopengBian Yuemin - Bladder cancer remains one of the most common malignancies of the urinary tract. Although the treatment landscape has expanded rapidly in recent years, gemcitabine still occupies a central position in intravesical treatment for non-muscle-invasive bladder cancer, in perioperative systemic therapy for muscle-invasive disease, and in platinum-based first-line regimens for advanced urothelial carcinoma. Yet the long-term benefit of gemcitabine is frequently curtailed by primary non-response or acquired resistance. In practice, this problem is often recognized only after radiographic progression or clear clinical deterioration has occurred. This review summarizes recent progress in bladder cancer therapy and translational research, with a particular emphasis on the biological basis and hierarchical evolution of gemcitabine resistance. We establish a 3-stage operational model of resistance, distinguishing: (1) early pharmacologic resistance driven by impaired drug uptake/activation or enhanced inactivation; (2) intermediate resistance driven by enhanced DNA damage repair, replication stress tolerance, and pro-survival autophagy signaling; and (3) late adaptive resistance driven by epithelial-mesenchymal transition (EMT), stemness maintenance, metabolic reprogramming, non-coding RNA-mediated epigenetic regulation, inflammatory microenvironmental remodeling, and extracellular vesicle-based intercellular transmission. These layers function as an interactive network, with sequential emergence under treatment pressure and parallel activation in context-dependent clinical settings. We stratify key mechanistic nodes (including the HYAL4-V1/CD44/JAK2-STAT3/CDA axis, AKR1C3, AP1M2-RAD54B, PRPF19-DDB1, AKT/mTOR signaling, Beclin-1-dependent autophagy, the MINCR/ZEB1/PHGDH axis, and IL-6-associated inflammatory states) by their clinical evidence quality and translational readiness, explicitly distinguishing preclinical discovery from clinically validated findings. Critically, most mechanistic findings remain at the preclinical or retrospective validation stage, with no markers yet approved for routine clinical use. Future work must prioritize longitudinal paired clinical samples, standardized analytic assays for dynamic biomarkers, and the integration of functional models (organoids, microfluidic systems), multi-omics technologies (single-cell sequencing, spatial transcriptomics), and liquid-biopsy approaches to translate mechanistic discoveries into clinically actionable predictive tools and therapeutic strategies. - Source: PubMed
Publication date: 2026/05/29
Jin MingCai ZhenzhenBu MingLiu JichengZhang Xiaojie - The vast majority of human malignancies are the result of sustained inflammatory responses. Nowadays, it is well-known that there is a substantial association between inflammation and cancer. The Salvia genus has garnered attention due to its richness of phytochemical profiles with anti-inflammatory and chemopreventive properties. Although the recognized therapeutic potential of Salvia species is recognized, there is considerable variation in their reported chemical composition, and less is known about their compositional differences. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of three Salvia species. This was followed by molecular docking of 218 compounds against KEAP1 (PDB: 4IQK) and iNOS (PDB: 1M8D), validated by positive controls. Network pharmacology, Protein-Protein Interaction (PPI), and enrichment analyses identified hub genes (TNF, CASP3, CASP8, PARP1, iNOS, EGFR, PPARG, AKR1C isoforms, and NQO1) linked to inflammatory and antioxidant signaling. Docking analysis predicted that several major compounds may exhibit dual binding affinities, supported by chemoinformatics, ADME, and toxicity predictions. Cirsimaritin was evaluated against AKR1C3 and PARP1 using molecular docking and 100-ns molecular dynamics simulations, representing different stability and interaction profiles between the two targets. The results indicate a dual binding activity, with Cirsimaritin exhibiting primary and stable interaction with AKR1C3 alongside a secondary, dynamic modulatory interaction with PARP1. Mostly bioactive compounds were predominantly found in Salvia multicaulis. The extracts were screened for their in vitro anti-inflammatory and chemoprevention activities. Preliminary experiments confirmed that S. multicaulis acts as an inducer of chemopreventive NAD(P)H: Quinone oxidoreductase 1 (NQO1) protein expression in a murine hepatoma (Hepa1c1c7) chemoprevention model. It also demonstrated the ability to inhibit the lipopolysaccharides (LPS)-induced nitric oxide (NO) production and iNOS protein expression in the RAW264.7 macrophage model. Furthermore, flavonoids and terpenoids were identified to be the major components in this extract, which might be responsible for anti-inflammatory and chemoprevention activities. Our results support the possible application of S. multicaulis in the treatment of human malignancies. - Source: PubMed
Publication date: 2026/06/09
Hamed Ahmed RAli Sherin KAbdel-Halim Sally ABata Shaymaa MHegazi Nesrine MMohamed Tarik AHegazy Mohamed-Elamir F