MGC4172 Blocking Peptide
- Known as:
- MGC4172 Blocking Peptide
- Catalog number:
- 33r-1951
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- MGC4172 Blocking Peptide
Related genes to: MGC4172 Blocking Peptide
- Gene:
- DHRS11 NIH gene
- Name:
- dehydrogenase/reductase 11
- Previous symbol:
- -
- Synonyms:
- MGC4172, SDR24C1
- Chromosome:
- 17q12
- Locus Type:
- gene with protein product
- Date approved:
- 2008-11-21
- Date modifiied:
- 2016-05-27
Related products to: MGC4172 Blocking Peptide
Related articles to: MGC4172 Blocking Peptide
- Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer lacking estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Among its heterogeneous subtypes, luminal androgen receptor-positive (LAR) TNBC is driven by androgen signaling and presents limited treatment options. We previously identified dehydrogenase/reductase SDR family member 11 (DHRS11) as a novel enzyme involved in androgen biosynthesis, and demonstrated that Kobochromone A (KC-A), a polyphenol isolated from Carex kobomugi, inhibited androgen-driven proliferation in LAR TNBC cells via DHRS11 inhibition and AR downregulation. In this study, we synthesized 23 structural derivatives of KC-A and identified WH23 as the most potent DHRS11 inhibitor (IC = 37 nM). Molecular docking and MM-PBSA analysis revealed that the 2'-hydroxy group of WH23 forms a hydrogen bond with His210 of DHRS11, which was validated by site-directed mutagenesis. WH23 suppressed AR mRNA and protein expression, reduced 11-ketodihydrotestosterone (11KDHT)-induced c-Myc expression, and inhibited proliferation of MDA-MB-453 cells. Additionally, WH23 inhibited PI3K/AKT signaling, reducing phosphorylation of PDK1, AKT, mTOR, and ERK. Capivasertib (Cap), a clinically approved pan-AKT inhibitor, induced DHRS11 expression in MDA-MB-453 cells. Although Cap and WH23 did not show synergistic cytotoxicity in parental cells, Cap-resistant (Cap-R) cells, which exhibited elevated DHRS11 and c-Myc expression, showed significant sensitivity to the combination. In Cap-R cells, the combination of Cap and WH23 significantly induced apoptosis, demonstrating a synergistic anticancer effect. These findings establish WH23 as a dual-acting compound targeting both androgen biosynthesis and AR signaling, with potential to overcome AKT inhibitor resistance in LAR TNBC. - Source: PubMed
Publication date: 2026/02/06
Miyamoto YuriHirai WakanaSaka TomofumiTanio MasatoshiKudo YudaiYoshino YutaNakagawa YusukeKobayashi NaoTakada SanaOkada TakuyaToyooka NaokiKandeel MahmoudTanaka NobutadaIkari AkiraEndo Satoshi - Breast cancer is the most common cancer in women, with triple-negative breast cancer (TNBC) accounting for approximately 20% of cases. TNBC lacks estrogen receptors (ER), progesterone receptors (PR), and epidermal growth factor receptor 2 (HER2) expression, which makes targeted therapies ineffective. The luminal androgen receptor (LAR) subtype of TNBC expresses androgen receptor (AR), highlighting the need for treatment strategies that target androgen signaling. Recently, the role of 11-oxygenated androgens, in addition to conventional androgens such as testosterone and dihydrotestosterone, in androgen-related diseases in women has gained increased attention. In this study, we investigated the involvement of 11-oxygenated androgens in LAR TNBC and explored the anti-androgenic effects of Kobochromone A (KC-A), a natural compound derived from Carex kobomugi. KC-A inhibits the androgen-synthesizing enzyme dehydrogenase/reductase short-chain dehydrogenase/reductase family member 11 (DHRS11) and suppresses AR expression. Using the AR-positive TNBC cell line MDA-MB-453, we demonstrated that 11-oxygenated androgens activate androgen signaling and promote cell proliferation. KC-A significantly inhibited androgen signaling by reducing nuclear AR localization and decreasing transmembrane protease, serine 2, and c-Myc expression. Furthermore, KC-A synergistically enhanced antiproliferative effects of the AKT inhibitor capivasertib (Cap), promoted apoptosis, and further suppressed AR expression. The primary therapeutic mechanisms of KC-A were identified as its dual actions: inhibition of DHRS11 and suppression of AR expression. These findings suggest that KC-A, either alone or in combination with AKT inhibitors, may offer a promising therapeutic strategy for LAR TNBC by targeting androgen signaling. Further studies are needed to confirm the efficacy and safety of KC-A in clinical applications. - Source: PubMed
Publication date: 2025/09/25
Tanio MasatoshiMiyamoto YuriSaka TomofumiKudo YudaiHayashi RiriKawano ShinyaYoshino YutaAbe NaohitoYamaguchi EijiArai YukiKashiwagi HirohitoOyama MasayoshiItoh AkichikaIkari AkiraEndo Satoshi - The pathogenesis of rectal cancer (RC) involves a variety of biological mechanisms; however, the prognostic significance of temperature-sensitive receptor (TRP) channels in RC patients remains unclear. This study aimed to explore the role of TRP-related genes in RC prognosis and their potential clinical implications. - Source: PubMed
Publication date: 2025/09/02
Wang XiaojunPeng JieqiongSong DongHou LijunWang QingshanZhou YanMa YananQiu ChenGuo QinpingWang Ganggang - In species with temperature-dependent sex determination (TSD), incubation temperature during a critical embryonic window directs gonadal fate, yet the underlying molecular mechanisms remain poorly understood. Here, we performed transcriptome sequencing of embryonic gonads from the red-eared slider turtle (Trachemys scripta elegans) incubated under male- and female-producing temperatures (MPT and FPT). Our analyses revealed numerous stage-specific differentially expressed genes and identified key candidates consistently upregulated under MPT or FPT conditions. Gene co-expression network analysis highlighted DHRS11 as a potential thermosensitive hub gene at MPT, and ATP2B4, a calcium transporter, as a hub under FPT, implicating calcium signaling in early sex determination. In addition, we uncovered widespread alternative splicing, including intron retention in the chromatin modifiers JARID2 and KDM6B, with CIRBP, a cold-inducible RNA-binding protein, as a potential upstream regulator. These findings suggest a role for transcriptional and post-transcriptional mechanisms, including calcium signaling and temperature-responsive splicing, in mediating TSD in reptiles. - Source: PubMed
Publication date: 2025/08/23
Fan JiaweiLi FangLou LingyuanHuang BaoyouChen QiranSun WeiGe ChutianWang Zongji - Heart failure (HF) is an important public health problem worldwide, and programmed cell death (PCD) plays a crucial role in its pathologic process. This study aims to identify the hub genes associated with HF through PCD in order to better understand the pathogenesis of HF and improve its diagnosis and treatment. - Source: PubMed
Publication date: 2025/04/10
Yuan Hua-JingYu HuiYu Yi-DingLiu Xiu-JuanLiu Wen-WenXue Yi-TaoLi Yan