Small molecule inhibitors of oncogenic miR-21

致癌 miR-21 的小分子抑制剂

基本信息

批准号：
10081975
负责人：
George A Calin
金额：
$ 24.91万
依托单位：
ITHAX PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-14 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10081975
关键词：
Advanced Development Advocate Affinity Animal Cancer Model Apoptotic Binding Biochemical Biogenesis Biotechnology Cancer Biology Cancer Center Cancer Model Capital Cell Line Cell model Cell physiology Cells Chemical Structure Chemistry Chronic Disease Clinical Collaborations Complex Data Development Drug Design Drug Kinetics Drug Targeting Eye Goals Growth Human Immunotherapeutic agent Immunotherapy In Vitro Inflammatory Lead Left Link Malignant - descriptor Malignant Neoplasms Malignant neoplasm of pancreas Metabolism MicroRNAs Molecular Oligonucleotides Oncogenes Oncogenic Oncology PTEN gene Patients Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacology Phase Phosphotransferases Positioning Attribute Privatization Production Property Proteins RNA Resistance Risk Safety Series Signal Transduction Small Business Innovation Research Grant Small Business Technology Transfer Research Structure Technical Expertise Technology Tissues Toxic effect Transcript Tumor Suppressor Proteins Universities University of Texas M D Anderson Cancer Center Untranslated RNA Washington Work absorption analog base cancer cell checkpoint therapy chemotherapy clinical candidate clinical development commercialization design drug discovery experience experimental study improved in vivo inhibitor/antagonist knock-down malignant stomach neoplasm mouse model non-oncogenic novel therapeutics outcome forecast overexpression pancreatic cancer cells preclinical development response biomarker small molecule small molecule inhibitor structural biology success tumor

项目摘要

Project Summary: Company development - Ithax Pharmaceuticals is a new spin-off biotechnology company located in Seattle and focused on developing small drug-like molecules that target non-coding RNAs in cancer and other chronic diseases. The experience of its founders’ spans drug design, RNA structure, cancer biology and biotech management, and includes the successful spin offs of several biotech companies. It gives the company an unmatched experience in the technological and commercial development of new companies in the RNA- oncology space. This Phase I STTR proposal lays out a series of experiments, beyond the scope of academic discovery, critical to advance and de-risk the commercialization plans of Ithax in the eyes of investors and pharmaceutical partners. Completion of this project will help the company fill gaps left in the academic discoveries of the founders by providing the data required to initiate medicinal chemistry optimization under a subsequent already planned phase II SBIR, and to successfully raise private capital needed for pre-clinical and clinical development. Technology - The proto-oncogenic non-coding RNA miR-21 is over-expressed in nearly every human tumor. Its over-expression is linked to unfavorable patient prognosis in multiple cancers and resistance to chemotherapeutic and immunotherapeutic treatment. Accumulating evidence in many cellular and multiple small animal models of cancers demonstrates that pharmacological inhibition of miR-21 would stop the progression of even late stage cancers, which are ‘addicted’ to this oncomiR, reduce chemo-resistance and potentiate checkpoint immunotherapy. Ithax’s first lead small molecule emerges from a collaboration between the University of Washington and the MD Anderson Cancer Center to identify new inhibitors of miRNA biogenesis. Preliminary data demonstrate that ITX-0052, a ‘Lipinski’ drug-like molecule with very safe in vitro pharmacological profile, inhibits miR-21 accumulation and reduces proliferation of gastric and pancreatic cancer cells with low M IC50 by binding directly to pre-miR-21. This project will establish the structural, biochemical and cellular mechanism of inhibition; and evaluate safety of administration, pharmacokinetics, pharmacodynamics and efficacy in murine models of gastric cancer.

项目概要：公司发展 - Ithax Pharmaceuticals 是一家新的衍生生物技术公司，位于西雅图和专注于开发针对癌症和其他慢性病的非编码 RNA 的小药物分子其创始人的经验涵盖药物设计、RNA 结构、癌症生物学和生物技术。管理，并包括几家生物技术公司的成功分拆，它为公司提供了一个机会。在 RNA 领域新公司的技术和商业开发方面拥有无与伦比的经验肿瘤学空间。第一阶段 STTR 提案列出了一系列超出学术发现范围的实验，在投资者和制药公司看来，这对于推进 Ithax 商业化计划并降低风险至关重要该项目的完成将帮助公司填补创始人学术发现中留下的空白。通过提供在后续已计划的情况下启动药物化学优化所需的数据 II 期 SBIR，并成功筹集临床前和临床开发所需的私人资本。技术 - 原癌非编码 RNA miR-21 在几乎所有人类肿瘤中过度表达。过度表达与多种癌症患者的不良预后和耐药性有关化疗和免疫治疗在许多细胞和多个小细胞中积累了证据。癌症动物模型表明，药物抑制 miR-21 可以阻止癌症的进展即使是晚期癌症，它们对这种 oncomiR“上瘾”，也会降低化疗耐药性并增强检查点免疫疗法。 Ithax 的第一个先导小分子是由华盛顿大学和 MD 安德森癌症中心确定了新的 miRNA 生物合成抑制剂，初步数据表明。 ITX-0052 是一种具有非常安全的体外药理学特征的“Lipinski”类药物分子，可抑制 miR-21 通过直接结合，抑制低 MIC50 胃癌和胰腺癌细胞的积累并减少其增殖该项目将建立 pre-miR-21 的结构、生化和细胞机制；评估胃病小鼠模型的给药安全性、药代动力学、药效学和疗效癌症。