AKR1C3 _ DDH3
- Known as:
- AKR1C3 _ DDH3
- Catalog number:
- GTX113586
- Product Quantity:
- 100 µg
- Category:
- -
- Supplier:
- ACR
- Gene target:
- AKR1C3 _ DDH3
Related genes to: AKR1C3 _ DDH3
- 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 _ DDH3
Related articles to: AKR1C3 _ DDH3
- Myxoglucamides, natural products recently isolated from Cystobacterineae sp., are featured by an unprecedented vinyl-substituted α-keto-γ-amino acid that is linked to a glycosylated 14-methyl-pentadecanoic acid. Thus, they unite elements from three biomolecular classes in a compact glycolipopeptide. To elucidate the biological relevance of this arrangement, we searched for molecular targets by activity-based protein profiling (ABPP)-although a phenotypic bioactivity has not been reported. An access to the compound class was established through the first total synthesis of myxoglucamide A in 11 steps. A proteome-wide ABPP study led to the identification of aldo-keto reductase 1C3 (AKR1C3) as the primary target of myxoglucamides in human cells. AKR1C3 is an oncogenic factor involved in prostaglandin and steroid synthesis, promoting the growth, proliferation, and metastasis of carcinoma cells. The functional inhibition of AKR1C3 by a competitive mechanism (IC = 1.61 µm) was validated in vitro, and 20 analogs provided structure-activity relationships and more potent analogs (IC = 181 nm). Biophysical interactions were quantified by thermal shift assays, and essential molecular protein-ligand interactions were characterized by X-ray crystallography at 2.0 Å resolution. The study implies that the search for targets of natural products is rewarding even in the absence of an initial phenotypic activity. - Source: PubMed
Publication date: 2026/08/10
Siemon ThomasMishra Vivek KZhao MingmingBüssow KonradPopoff AlexanderFu ChengzhangMüller RolfJänsch LotharBlankenfeldt WulfBrönstrup Mark - This study investigated the preliminary role of γ-oryzanol (γ-O) against breast cancer through computational and in vitro analyses. Reference protein set (RPS) and functional enrichment set (FES) proteins were identified and subjected to network pharmacology. Pharmacogenomics analysis assessed expression profiles and survival associations. Molecular docking of γ-O with PIK3CA, AKT1, AKR1C3, ESR1, and MAPK1 was performed, followed by molecular dynamics (MD) simulation of the γ-O-PIK3CA complex. Brine shrimp lethality assay (BSLA) evaluated the effect of γ-O on nauplii survival and percentage lethality. Allium cepa root tip assay (ACARTA) assessed the effect of γ-O in number and length of roots. Cell viability assay evaluated MCF-7 cell viability after γ-O treatment. Target validation and network pharmacology suggested the relevance of RPS and FES with cancer-associated pathways. Pharmacogenomics analysis highlighted FES overexpression with reduced survival associations and cancer progression. Molecular docking predicted interaction of γ-O with PIK3CA (- 9.1 kcal/mol), AKT1 (- 7.2 kcal/mol), AKR1C3 (- 12.3 kcal/mol), ESR1 (- 8.3 kcal/mol), and MAPK1 (- 8.9 kcal/mol). MD simulation indicated the stability of γ-O-PIK3CA complex. γ-O treatment significantly (P-value < 0.05) reduced nauplii survival and increased percentage lethality. The number and length of roots reduced significantly (P-value < 0.05) in γ-O-treated roots. γ-O produced a significant (P-value < 0.05) concentration-dependent reduction in cell viability (half-maximal inhibitory concentration = 352.57 ± 48.51 µg/mL). BSLA, ACRTA, and cell viability assay demonstrated preliminary cytotoxic, anti-mitotic, and anti-proliferative effects of γ-O, aligned with computational target and interaction analyses. Further studies are required to validate its mechanistic relevance against breast cancer. - Source: PubMed
Publication date: 2026/07/29
Sukhadia MahimaPatel HoneyGupta AdarshJawarkar RahulShah UmangPatel AlkeshkumarRaval Keval - ObjectiveTo investigate whether naringin enhances the chemosensitivity of nasopharyngeal carcinoma-derived CNE2 cells to paclitaxel and identify potential molecular mediators.MethodsCNE2 cells were treated with naringin alone or in combination with paclitaxel, cisplatin, or 5-fluorouracil. Cell viability, proliferation, and migration were assessed using cell counting kit-8 and Transwell assays. Transcriptomic profiling followed by bioinformatic analysis of Gene Expression Omnibus datasets (GSE53819, GSE12452, and GSE102349) was performed to identify nasopharyngeal carcinoma prognosis-related genes. overexpression was established via lentiviral transduction, and pharmacological inhibition was performed using ASP9521. mRNA and protein expression were validated using reverse transcription quantitative polymerase chain reaction and Western blot analysis.ResultsNaringin (160 μM) demonstrated a trend toward reducing the half-maximal inhibitory concentration of paclitaxel from 10.52 to 8.04 nM; however, it did not significantly alter sensitivity to cisplatin or 5-fluorouracil. Combined treatment with 2 nM paclitaxel and 160 μM naringin synergistically suppressed CNE2 proliferation and migration compared with that using either agent alone ( < 0.05). Bioinformatic analysis revealed that high expression was correlated with improved survival in patients with nasopharyngeal carcinoma ( < 0.05), whereas high , , , and expressions were correlated with poorer outcomes. Reverse transcription quantitative polymerase chain reaction confirmed that both naringin and paclitaxel upregulated mRNA, with the combination producing the strongest effect. Gain-of-function studies demonstrated that overexpression significantly enhanced paclitaxel sensitivity, with half-maximal inhibitory concentration values decreasing from 13.63 to 6.994 nM in CNE2 cells and from 8.534 to 4.668 nM in CNE1 cells. Furthermore, the specific inhibitor, ASP9521, significantly attenuated the synergistic anti-proliferative and anti-migratory effects of paclitaxel + naringin in CNE2 cells, confirming that naringin enhances chemosensitivity to paclitaxel by upregulating AKR1C3 expression.ConclusionsNaringin sensitizes CNE2 cells to paclitaxel, potentially via upregulation. This flavonoid may represent a low-toxicity adjunct to enhance the efficacy of paclitaxel in nasopharyngeal carcinoma. - Source: PubMed
Publication date: 2026/07/29
Huang ZhenheQiu YumeiLiu FangchuChen XiaoliWang Xintao - Small molecule-drug conjugates (SMDCs) represent an emerging prodrug strategy for precision targeted therapy. In this study, we developed a series of cathepsin B (CTSB)-activated SMDCs targeting Aldo-keto reductase family 1 member C3 (AKR1C3). Among these conjugates, SM-27 was identified as the optimized compound, which exhibited excellent inhibitory activity against AKR1C3 with an inhibitory concentration value of 9 ± 2 nM and could efficiently release the payload gemcitabine under the mediation of CTSB. The antitumor activity of SM-27 was dually dependent on the expression of AKR1C3 and CTSB, allowing it to precisely recognize and eliminate tumor cells with low toxicity to normal cells. In vivo xenograft tumor assays with SM-27 showed significantly superior tumor inhibitory efficacy to gemcitabine with markedly lower off-target toxicity. In conclusion, this study proposes a novel design strategy for SMDCs targeting AKR1C3, which provides a highly promising research approach to address the off-target issue in chemotherapy. - Source: PubMed
Wang XiaolongGuo CanLiu YimengHan BingjieZhang LuLiu ZongliangChen YaoSun Haopeng - Liver cancer, particularly hepatocellular carcinoma (HCC), remains a leading cause of cancer-related mortality worldwide. Chlorogenic acid (CGA), a dietary polyphenol abundant in coffee and plant-based foods, has emerged as a potential bioactive compound with anticancer and hepatoprotective properties. This systematic review aimed to evaluate the effects of CGA on liver cancer, focusing on its molecular mechanisms and potential synergistic or antagonistic interactions. - Source: PubMed
Publication date: 2026/07/17
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