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 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- 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
-
Small Molecule Inhibitors Targeting Key Proteins in the DNA Damage Response for Cancer Therapy
Current Medicinal Chemistry Recent Advances in Enone and NO-Releasing Derivatives of Oleanolic Acid with Anti-cancer Activity
Mini-Reviews in Organic Chemistry Current Status Of Short Synthetic Peptides As Vaccines
Medicinal Chemistry Molecular Targets for Epigenetic Therapy of Cancer
Current Pharmaceutical Biotechnology Targeted Tumor Therapies at a Glance
Current Drug Targets TRIM45 Suppresses the Development of Non-small Cell Lung Cancer
Current Molecular Medicine Inhibiting HSP90 to Treat Cancer: A Strategy in Evolution
Current Molecular Medicine Mechanism of Drug Sensitivity and Resistance in Melanoma
Current Cancer Drug Targets Histone Modifications as Molecular Targets in Nasopharyngeal Cancer
Current Medicinal Chemistry Medullary Thyroid Cancer: A Promising Model for Targeted Therapy
Current Molecular Medicine Synthesis and Evaluation of Vascular Endothelial Growth Factor Receptor-2 Inhibitory Activity of 6,7-Dimethoxycinnoline Derivatives
Letters in Drug Design & Discovery Modulation of Doxorubicin Mediated Growth Inhibition of Hepatocellular Carcinoma Cells by Platelet Lysates
Anti-Cancer Agents in Medicinal Chemistry iNOS: A Potential Therapeutic Target for Malignant Glioma
Current Molecular Medicine Bleomycin and its Role in Inducing Apoptosis and Senescence in Lung Cells - Modulating Effects of Caveolin-1
Current Cancer Drug Targets Lysosomotropic Drugs: Pharmacological Tools to Study Lysosomal Function
Current Drug Metabolism Graphical Abstracts:
Current Nanoscience A Virtual Screening Approach for the Identification of High Affinity Small Molecules Targeting BCR-ABL1 Inhibitors for the Treatment of Chronic Myeloid Leukemia
Current Topics in Medicinal Chemistry Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems
Recent Patents on Anti-Cancer Drug Discovery Recent Patents in Pulmonary Delivery of Macromolecules
Recent Patents on Drug Delivery & Formulation Heat Shock Proteins: Therapeutic Drug Targets for Chronic Neurodegeneration?
Current Pharmaceutical Biotechnology