Abstract
Hypoxia-inducible factor-1α (HIF-1α) and signal transducer and activator of transcription 3 (STAT3) are transcription factors and are activated in response to hypoxia. Both HIF-1α and STAT3 regulate various aspects of cancer biology such as cell survival, proliferation, angiogenesis etc. and are constitutively expressed in a wide range of human cancers. In the last decade, over expression of HIF-1α and STAT3 has been demonstrated in many common human cancers, thereby emerging as highly compelling anticancer targets for drug discovery. We herein report the design and synthesis of new imidazopyridine based potent dual inhibitors of HIF-1α and STAT3 pathways. The lead compound of this series P3971 has been identified as a potent inhibitor of HIF-1α (200 nM) and STAT3 (350 nM) with significant antiproliferative activity against various cancer cell lines. Moreover, P3971 was also found to be orally efficacious in HCT116 (colon cancer) and H460 (lung cancer) xenograft mice models.
Keywords: Anticancer, drug discovery, HIF-1α, STAT3, imidazopyridine.
Anti-Cancer Agents in Medicinal Chemistry
Title:Discovery of P3971 an Orally Efficacious Novel Anticancer Agent Targeting HIF-1α and STAT3 Pathways
Volume: 13 Issue: 9
Author(s): Pallavi Godse, Pramod Kumar, Nilambari Yewalkar, Vijaykumar Deore, Manoj Lohar, Ramswaroop Mundada, Amol Padgaonkar, Sonal Manohar, Asavari Joshi, Dimple Bhatia, Nikesh Desai, Anagha Damre, Mandar Bhonde, Kalpana Joshi, Rajiv Sharma and Sanjay Kumar
Affiliation:
Keywords: Anticancer, drug discovery, HIF-1α, STAT3, imidazopyridine.
Abstract: Hypoxia-inducible factor-1α (HIF-1α) and signal transducer and activator of transcription 3 (STAT3) are transcription factors and are activated in response to hypoxia. Both HIF-1α and STAT3 regulate various aspects of cancer biology such as cell survival, proliferation, angiogenesis etc. and are constitutively expressed in a wide range of human cancers. In the last decade, over expression of HIF-1α and STAT3 has been demonstrated in many common human cancers, thereby emerging as highly compelling anticancer targets for drug discovery. We herein report the design and synthesis of new imidazopyridine based potent dual inhibitors of HIF-1α and STAT3 pathways. The lead compound of this series P3971 has been identified as a potent inhibitor of HIF-1α (200 nM) and STAT3 (350 nM) with significant antiproliferative activity against various cancer cell lines. Moreover, P3971 was also found to be orally efficacious in HCT116 (colon cancer) and H460 (lung cancer) xenograft mice models.
Export Options
About this article
Cite this article as:
Godse Pallavi, Kumar Pramod, Yewalkar Nilambari, Deore Vijaykumar, Lohar Manoj, Mundada Ramswaroop, Padgaonkar Amol, Manohar Sonal, Joshi Asavari, Bhatia Dimple, Desai Nikesh, Damre Anagha, Bhonde Mandar, Joshi Kalpana, Sharma Rajiv and Kumar Sanjay, Discovery of P3971 an Orally Efficacious Novel Anticancer Agent Targeting HIF-1α and STAT3 Pathways, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (9) . https://dx.doi.org/10.2174/18715206113136660341
DOI https://dx.doi.org/10.2174/18715206113136660341 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Editorial [Hot topic: Cell Adhesion Molecules: Structure, Function, Drug Design, and Biomaterials (Executive Editor: Seetharama D. Satyanarayanajois)]
Current Pharmaceutical Design Emerging Vascular Risk Factors in Women: Any Differences from Men?
Current Medicinal Chemistry Synthesis and in vitro Evaluation of the Anticancer Potential of New Aminoalkanol Derivatives of Xanthone
Anti-Cancer Agents in Medicinal Chemistry The Lung Disease of Rheumatoid Arthritis
Current Respiratory Medicine Reviews Antioxidant Effect of a Nitrated Cyclic Nucleotide Functioning as an Endogenous Electrophile
Current Topics in Medicinal Chemistry Optical and Multimodal Peptide-Based Probes for In Vivo Molecular Imaging
Anti-Cancer Agents in Medicinal Chemistry Phosphodiesterase Type 5 Inhibitors: Unmet Needs
Current Pharmaceutical Design Identification of Functional Peptides from Natural and Synthetic Products on Their Anticancer Activities by Tumor Targeting
Current Medicinal Chemistry Autophagy: Molecular Mechanisms and their Implications for Anticancer Therapies
Current Cancer Drug Targets Inhibitory Effect on Replicative DNA Polymerases, Human Cancer Cell Proliferation, and In Vivo Anti-Tumor Activity by Glycolipids from Spinach
Current Medicinal Chemistry Theoretical Analysis of the Binding of Potential Inhibitors to Protein Kinases MK2 and MK3
Medicinal Chemistry Arene ruthenium(II) Complexes: The Promising Chemotherapeutic Agent in Inhibiting the Proliferation, Migration and Invasion
Mini-Reviews in Medicinal Chemistry TXNL1 Induces Apoptosis in Cisplatin Resistant Human Gastric Cancer Cell Lines
Current Cancer Drug Targets Biodistribution and Pharmacokinetics of I-131 Labelled 4- Iodophenylacetic Acid
Current Radiopharmaceuticals Regulatory Cross Talks of Bone Cells, Hematopoietic Stem Cells and the Nervous System Maintain Hematopoiesis
Inflammation & Allergy - Drug Targets (Discontinued) Cytosine Methyltransferases as Tumor Markers
Current Genomics Electrochemical Nano-biosensors as Novel Approach for the Detection of Lung Cancer-related MicroRNAs
Current Molecular Medicine Status of Flavonols as P-Glycoprotein Inhibitors in Cancer Chemotherapy
Current Cancer Therapy Reviews Deep Learning in the Quest for Compound Nomination for Fighting COVID-19
Current Medicinal Chemistry Mechanisms of Tumor Cell Necrosis
Current Pharmaceutical Design