Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to impaired endothelial function and dysregulation of the angiotensin system that occurs during the preeclamptic pregnancy and persists postpartum, despite the remission of clinical symptoms. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage caused by reduced endothelial function in women who have had preeclampsia compared to women who had a healthy pregnancy. Identification of these mechanisms and treatment strategies may lead to better clinical management of cardiovascular disease risk in these women.
The purpose of this study is to examine the microvascular differences in women who have had preeclampsia following activation of protective angiotensin receptors in the skin. This will help increase understanding of the mechanisms of angiotensin II receptors in these women, and how activation of these receptors may restore microvascular function.
In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) the investigators examine the blood vessels in a dime-sized area of the skin.

开始日期2023-06-28

申办/合作机构

University of Iowa

100 项与 Compound 21(UIOWA) 相关的临床结果

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100 项与 Compound 21(UIOWA) 相关的转化医学

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100 项与 Compound 21(UIOWA) 相关的专利（医药）

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项与 Compound 21(UIOWA) 相关的文献（医药）

2026-02-01·JOURNAL OF MOLECULAR HISTOLOGY

Protective effects of buloxibutid and empagliflozin on hypertension-induced cardiac and vascular injury in rats

Article

作者: Parlakpinar, Hakan ; Dogru, Feyzi ; Karaca, Elif ; Kucukakcali, Zeynep ; Acet, Ahmet ; Colak, Mehmet ; Ozhan, Onural

This study aims to see the individual and combined effects of Angiotensin II type 2 (AT2) receptor agonist buloxibutid (also known as Compound 21 or C21) and sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin (EMPA) on effects of hypertension (HT), which is common today, on the heart, and vascular tissue. Male rats of the Sprague Dawley were divided into 5 groups: Control (C) group, HT group, HT + C21 group, HT + EMPA group and HT + C21 + EMPA group. After the protocol was completed, hemodynamic measurements were taken and heart and aorta tissues were evaluated biochemically, histopatologically and immunohistochemically. When the mean blood pressure (BP) values were compared, the mean BP of the HT group increased significantly compared to the C group (p < 0.05). Superoxide dismutase, glutathione and glutathione peroxidase activities in the heart, glutathione and catalase activities in the descending aorta were significantly higher in all treated groups compared to the HT group (p < 0.05). In the HT + C21 + EMPA group, histopathological damage score in hematoxylin-eosin (HE) stained heart sections compared to the HT group showed a decrease in tissue damage but cell infiltration was still observed. When HE staining method was applied, it was determined that the thoracic aorta sections in group C had normal histologic structure. In the HT group, dilatation in some parts and irregularities in elastic lamellae were observed. It was observed that the treated groups were similar to group C. When considering the individual and combined effects of C21 and EMPA, positive results on heart and vascular tissue were observed by hemodynamic, biochemical and histopathological analyses.

2025-06-01·BIOORGANIC CHEMISTRY

Discovery of a novel Thiazole amide inhibitor of Inflammasome and Pyroptosis pathways

Article

作者: Wang, Ke ; Yu, Quanwei ; Chen, Zhiping ; Wang, Yuxi ; Bai, Chenli ; Dai, Zhen ; Li, Yong ; Ding, Jianjun ; Liao, Jihong

Upon the activation of inflammasomes, inflammatory caspases cleave and activate gasdermin D (GSDMD), leading to pore formation that causes cell membrane rupture and amplifies downstream inflammatory responses. Dysregulated inflammasome activation and pyroptosis signaling pathways are implicated in numerous inflammatory diseases. In our work, a set of novel thiazole amide compounds with inhibitory activity against NLRP3 inflammasome-induced pyroptosis was identified. Of all the compounds tested, compound 21 demonstrated the most potent anti-pyroptotic effects. It suppressed GSDMD cleavage and decreased IL-1β and lactate dehydrogenase (LDH) release in a concentration-dependent manner. Compound 21 bound to NLRP3 protein and increased the thermal stability of NLRP3 concentration-dependently. The molecular docking and dynamics simulations revealed that compound 21 binds to the NLRP3 protein's active site, suppressing inflammasome activation. Further investigations showed that compound 21 also partially blocked upstream NF-κB signaling and downstream GSDMD N-terminal domain (GSDMD-NT) oligomerization, which explains its broad inhibitory effects on pyroptosis driven by multiple inflammasomes. Overall, this study presents a promising thiazole amide compound with inhibitory activity against inflammasome activation and subsequent pyroptosis, warranting further exploration.

2025-05-01·HYPERTENSION

Reduced AT ₂ R Signaling Contributes to Endothelial Dysfunction After Preeclampsia

Article

作者: Santillan, Mark K. ; Schwartz, Kelsey S. ; Stanhewicz, Anna E. ; Jalal, Diana I. ; Sun, Mingyao

BACKGROUND::

Women who had preeclampsia (a history of preeclampsia) have a >4-fold risk of developing cardiovascular disease compared with women who had an uncomplicated pregnancy (history of healthy pregnancy). Despite the remission of clinical symptoms after pregnancy, vascular endothelial dysfunction persists postpartum, mediated in part by exaggerated Ang II (angiotensin II)–mediated constriction. However, the role of vasodilatory AT 2 Rs (Ang II type 2 receptors) in this dysfunction is unknown. We examined the functional role of AT 2 R in the microvasculature postpartum and whether acute activation of AT 2 R improves microvascular endothelial function after preeclampsia.

METHODS::

Overall, 24 women (n=12/group) participated. We measured cutaneous vascular conductance responses to (1) graded infusion of compound 21 (AT 2 R agonist; 10 −14 –10 −8 M) alone or with NG-nitro-l-arginine methyl ester (NO synthase inhibitor; 15 mM) and (2) a standardized local heating protocol in control and 10 −11 M compound 21–treated sites. Expression of Ang II receptor subtypes I and II in biopsied venous endothelial cells was quantified using immunofluorescence.

RESULTS::

AT 2 R-mediated dilation ( P <0.01) and the NO-dependent contribution ( P =0.003) of this response were reduced in women with a history of preeclampsia. Endothelial AT 2 R expression was lower in women with a history of preeclampsia ( P <0.01), but there were no differences in endothelial AT 1 R (Ang II type 1 receptor) expression ( P >0.05). Acute activation of AT 2 R during local heating improved endothelium ( P <0.01) and NO-dependent ( P <0.01) dilation in women with a history of preeclampsia but had no effect in women with a history of healthy pregnancy (both P >0.05).

CONCLUSIONS::

Reductions in AT 2 R-mediated dilation contribute to attenuated or impaired endothelial function in women who had a pregnancy complicated by preeclampsia. Furthermore, AT 2 R activation may improve endothelial function through NO-dependent mechanisms in otherwise healthy women who had preeclampsia before the onset of cardiovascular disease.

REGISTRATION::

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05937841.

项与 Compound 21(UIOWA) 相关的新闻（医药）

2025-11-02

·DrugFinder

新药管线第7期：从肿瘤到神经疾病：10个突破性候选分子盘点

靶点涵盖 DNA修复（FEN1、MYC）、受体调控（P2X7、DRD2、OXTR）、以及离子通道（α2δ亚基）、代谢与炎症靶点（ZBTB7A、FabI、edema factor）等疾病领域从肿瘤、神经病理性疼痛、哮喘与炎症，到感染性疾病、贫血、罕见病（如Prader-Willi综合征）这些分子由 Artios、Merck、Jazz、Haisco、Debiopharm、Acadia 等全球头部药企与研究机构联合推动 🧬 1. MSC778 | FEN1抑制剂靶点： FEN1疾病：肿瘤前临床研究公司： Artios Pharma、Merck Healthcare从金属螯合片段出发，经结构优化获得，展示出强效DNA修复通路抑制潜力。🧠 2. ONC206 | ClpP & DRD2双靶点疾病：胶质母细胞瘤、肉瘤公司： Oncoceutics、Jazz Pharmaceuticals具脑穿透性，兼具ClpP激动与多巴胺受体拮抗活性，被誉为下一代中枢系统抗癌药原型。⚡ 3. crisugabalin (HSK16149) | 钙通道α2δ配体疾病：中枢与外周神经病理性疼痛公司：海思科制药（成都）源自加巴喷丁骨架的结构优化，正在进行III期临床，为糖尿病性神经痛提供新方案。🧫 4. UB-MBX-46 | P2X7受体拮抗剂疾病：炎症相关疾病机构：俄勒冈健康与科学大学从文献先导化合物出发，通过结构优化获得新型变构拮抗剂。☣️ 5. compound 21 | 水肿因子抑制剂疾病：炭疽感染公司： Hawaii Biotech首个基于核苷类EF抑制剂的共价改良版本，为炭疽毒素防治提供新方向。💊 6. Debio 1453 | Fabl抑制剂疾病：淋病公司： Debiopharm（瑞士洛桑）针对耐药淋病菌的全新机制抗菌药，从SBDD与SAR协同优化获得。🔬 7. compound 15 | MYC抑制剂疾病：肿瘤机构：安徽中医药大学通过骨架跃迁获得的MYC抑制分子，探索癌基因靶向的前临床潜力。💨 8. dexpramipexole | 嗜酸细胞调节剂疾病：哮喘、肌萎缩侧索硬化症（ALS）公司： Knopp Biosciences从ALS候选药物再开发而来，III期临床显示显著炎症改善。💗 9. carbetocin (ACP-101) | 催产素受体激动剂疾病： Prader-Willi综合征公司： Acadia Pharma、Ferring Pharma鼻喷制剂形式改善暴食行为，正在III期试验中。🧩 10. SH6 | ZBTB7A降解剂疾病：镰状细胞贫血、地中海贫血机构： Brigham & Women’s Hospital基于靶向蛋白降解策略的非-IMiD分子，为血红蛋白疾病带来新希望。参考文献 https://drughunter.com/molecules-of-the-month/september-2025 相关阅读全球新药管线第6期：多款候选药物挺进Ⅲ期，临床迎来新突破新药管线第5期：全球10个最值得关注的新药分子新药研发第4期：全球新药热门靶点分子进展盘点 Revolution Medicines ｜发布KRAS G12D靶向临床新进展：组合疗法100%癌症患者缓解

临床3期临床2期申请上市寡核苷酸

100 项与 Compound 21(UIOWA) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
先兆子痫	临床1期	美国	University of Iowa	2023-06-28

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Phase I (ESH2017)	临床1期	-	-	Compound 21 (C21) 0.3 mg	壓積顧醖觸顧築憲壓鏇(淵遞壓窪憲觸構網製鏇) = 齋繭繭鹹蓋齋餘築觸膚願鏇製築選廠餘獵壓壓 (衊簾衊遞鹹糧願艱遞鹹 ) 更多	积极	2017-09-01
				Compound 21 (C21) 1 mg	壓積顧醖觸顧築憲壓鏇(淵遞壓窪憲觸構網製鏇) = 壓網積醖範繭築膚製鹹願鏇製築選廠餘獵壓壓 (衊簾衊遞鹹糧願艱遞鹹 ) 更多