2. Academic Validation
  3. Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

  • J Clin Med. 2019 Nov 2;8(11):1847. doi: 10.3390/jcm8111847.
Byung-Hak Kim 1 2 3,  Haeri Lee 4 5,  Yeonghun Song 6,  Joon-Suk Park 7,  Changdev G Gadhe 8,  Jiwon Choi 9,  Chung-Gi Lee 10,  Ae Nim Pae 11 12,  Sanghee Kim 13,  Sang-Kyu Ye 14 15 16 17
Affiliations

Affiliations

  • 1 Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. protein0826@snu.ac.kr.
  • 2 Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea. protein0826@snu.ac.kr.
  • 3 CYTUS H&B Corporation, Cheongju 28159, Korea. protein0826@snu.ac.kr.
  • 4 Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. hrlee519@snu.ac.kr.
  • 5 Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea. hrlee519@snu.ac.kr.
  • 6 College of Pharmacy, Seoul National University, Seoul 08826, Korea. song2@snu.ac.kr.
  • 7 Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea. song2@snu.ac.kr.
  • 8 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, Korea. gadhe.changdev@gmail.com.
  • 9 Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. c_jiwon@hotmail.com.
  • 10 CYTUS H&B Corporation, Cheongju 28159, Korea. cglee2020@gmail.com.
  • 11 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, Korea. anpae@kist.re.kr.
  • 12 Division of Bio-Medical Science &Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Korea. anpae@kist.re.kr.
  • 13 College of Pharmacy, Seoul National University, Seoul 08826, Korea. pennkim@snu.ac.kr.
  • 14 Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. sangkyu@snu.ac.kr.
  • 15 Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea. sangkyu@snu.ac.kr.
  • 16 Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea. sangkyu@snu.ac.kr.
  • 17 Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, Seoul 03080, Korea. sangkyu@snu.ac.kr.
PMID: 31684051 DOI: 10.3390/jcm8111847
Abstract

Persistently activated STAT3 is a promising target for a new class of Anticancer drug development and Cancer therapy, as it is associated with tumor initiation, progression, malignancy, drug resistance, Cancer stem cell properties, and recurrence. Here, we discovered 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117) as a small-molecule inhibitor of STAT3 to be used in STAT3-targeted Cancer therapy. ODZ10117 targeted the SH2 domain of STAT3 regardless of other STAT family proteins and upstream regulators of STAT3, leading to inhibition of the tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3. The inhibitory effect of ODZ10117 on STAT3 was stronger than the known STAT3 inhibitors such as S3I-201, STA-21, and nifuroxazide. ODZ10117 suppressed the migration and invasion, induced Apoptosis, reduced tumor growth and lung metastasis, and extended the survival rate in both in vitro and in vivo models of breast Cancer. Overall, we demonstrated that ODZ10117 is a novel STAT3 Inhibitor and may be a promising agent for the development of Anticancer drugs.

Keywords

3-(2,4-Dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117); SH2 domain; STAT3; cell-based high-throughput screening; structure-based computational database screening; targeted therapy.

Figures
Products
Inhibitors & Agonists
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13919
    98.85%, STAT3 抑制剂
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