Xiao-Hong Zhou, Susanne Prothon, Engin Liathdale, Nicola Ferrari, Kebria Hezaveh, Zhi Liu, Szilard Nemes, Joachim Almquist, Michael L Williams, Olami Sobande, Christer Gottfridsson, Bernadette R Gochuico, Adam Platt, Zach Brohawn, Maria G Belvisi, Ronald Goldwater, Ellinor Hornberg, Caroline A Owen
{"title":"一项评估豪猪抑制剂AZD5055的安全性、耐受性和药代动力学的i期研究。","authors":"Xiao-Hong Zhou, Susanne Prothon, Engin Liathdale, Nicola Ferrari, Kebria Hezaveh, Zhi Liu, Szilard Nemes, Joachim Almquist, Michael L Williams, Olami Sobande, Christer Gottfridsson, Bernadette R Gochuico, Adam Platt, Zach Brohawn, Maria G Belvisi, Ronald Goldwater, Ellinor Hornberg, Caroline A Owen","doi":"10.1016/j.isci.2025.112602","DOIUrl":null,"url":null,"abstract":"<p><p>Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers. Secondary and exploratory objectives were the pharmacokinetics and pharmacodynamics of AZD5055, respectively. Sixty healthy volunteers were randomized to receive placebo or AZD5055 in single ascending doses of 7, 20, or 40 mg (part 1), or multiple ascending doses of 5, 15, or 20 mg once daily over 14 consecutive days of dosing (Part 2). AZD5055 was safe and well tolerated in both study parts. AZD5055 exposure increased dose-proportionally with a pharmacokinetic profile enabling once daily dosing. AZD5055 effectively inhibited Wnt signaling in skin, hair follicles, and serum samples. Thus, AZD5055 has therapeutic potential in Wnt-driven fibrotic diseases and cancers.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"112602"},"PeriodicalIF":4.6000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177174/pdf/","citationCount":"0","resultStr":"{\"title\":\"A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055.\",\"authors\":\"Xiao-Hong Zhou, Susanne Prothon, Engin Liathdale, Nicola Ferrari, Kebria Hezaveh, Zhi Liu, Szilard Nemes, Joachim Almquist, Michael L Williams, Olami Sobande, Christer Gottfridsson, Bernadette R Gochuico, Adam Platt, Zach Brohawn, Maria G Belvisi, Ronald Goldwater, Ellinor Hornberg, Caroline A Owen\",\"doi\":\"10.1016/j.isci.2025.112602\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers. Secondary and exploratory objectives were the pharmacokinetics and pharmacodynamics of AZD5055, respectively. Sixty healthy volunteers were randomized to receive placebo or AZD5055 in single ascending doses of 7, 20, or 40 mg (part 1), or multiple ascending doses of 5, 15, or 20 mg once daily over 14 consecutive days of dosing (Part 2). AZD5055 was safe and well tolerated in both study parts. AZD5055 exposure increased dose-proportionally with a pharmacokinetic profile enabling once daily dosing. AZD5055 effectively inhibited Wnt signaling in skin, hair follicles, and serum samples. Thus, AZD5055 has therapeutic potential in Wnt-driven fibrotic diseases and cancers.</p>\",\"PeriodicalId\":342,\"journal\":{\"name\":\"iScience\",\"volume\":\"28 6\",\"pages\":\"112602\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177174/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"iScience\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1016/j.isci.2025.112602\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/20 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.isci.2025.112602","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/20 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055.
Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers. Secondary and exploratory objectives were the pharmacokinetics and pharmacodynamics of AZD5055, respectively. Sixty healthy volunteers were randomized to receive placebo or AZD5055 in single ascending doses of 7, 20, or 40 mg (part 1), or multiple ascending doses of 5, 15, or 20 mg once daily over 14 consecutive days of dosing (Part 2). AZD5055 was safe and well tolerated in both study parts. AZD5055 exposure increased dose-proportionally with a pharmacokinetic profile enabling once daily dosing. AZD5055 effectively inhibited Wnt signaling in skin, hair follicles, and serum samples. Thus, AZD5055 has therapeutic potential in Wnt-driven fibrotic diseases and cancers.
期刊介绍：
Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results.
We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
