Abstract
The inorganic arsenic derivative arsenic trioxide (ATO) has proven to be highly efficacious in patients with acute promyelocytic leukemia (APL) and has been associated with complete cytogenetic response in most treated patients diagnosed with this disease. This is due to ATOs direct effect on PML-RARα oncoprotein patognomonic for APL. ATO has shown moderate activity against certain other hematologic and solid organ malignancies but is also associated with significant toxicities, especially when used at higher doses. The development of orally bioavailable organic arsenic derivatives (OAD) offering improved toxicity profiles and better efficacy may expand the use of arsenic derivatives in hematologic malignancies and solid tumors. The favorable in vivo carcinostatic activity of S-dimethylarsino-thioglucose, the first OAD synthesized in murine leukemia models by our group in 1975, set the stage for our efforts to develop OADs. Unfortunately, the program remained dormant for almost two decades. The success of ATO in APL in the late 1990s re-ignited the interest in the use of OADs in cancer chemotherapy. This review describes the chemical development of OADs and summarizes the clinical development of a promising lead compound, Darinaparsin (ZIO-101; SGLU; S-dimethylarsino-glutathione), for the treatment of a variety of cancers.
Keywords: Darinaparsin, SGLU, ZIO-101, S-dimethylarsino-glutathione, arsenic trioxide, leukemia
Anti-Cancer Agents in Medicinal Chemistry
Title: Chemical and Clinical Development of Darinaparsin, a Novel Organic Arsenic Derivative
Volume: 8 Issue: 8
Author(s): Alfonso Quintas-Cardama, Srdan Verstovsek, Emil Freireich, Hagop Kantarjian, Yi Wen Chen and Ralph Zingaro
Affiliation:
Keywords: Darinaparsin, SGLU, ZIO-101, S-dimethylarsino-glutathione, arsenic trioxide, leukemia
Abstract: The inorganic arsenic derivative arsenic trioxide (ATO) has proven to be highly efficacious in patients with acute promyelocytic leukemia (APL) and has been associated with complete cytogenetic response in most treated patients diagnosed with this disease. This is due to ATOs direct effect on PML-RARα oncoprotein patognomonic for APL. ATO has shown moderate activity against certain other hematologic and solid organ malignancies but is also associated with significant toxicities, especially when used at higher doses. The development of orally bioavailable organic arsenic derivatives (OAD) offering improved toxicity profiles and better efficacy may expand the use of arsenic derivatives in hematologic malignancies and solid tumors. The favorable in vivo carcinostatic activity of S-dimethylarsino-thioglucose, the first OAD synthesized in murine leukemia models by our group in 1975, set the stage for our efforts to develop OADs. Unfortunately, the program remained dormant for almost two decades. The success of ATO in APL in the late 1990s re-ignited the interest in the use of OADs in cancer chemotherapy. This review describes the chemical development of OADs and summarizes the clinical development of a promising lead compound, Darinaparsin (ZIO-101; SGLU; S-dimethylarsino-glutathione), for the treatment of a variety of cancers.
Export Options
About this article
Cite this article as:
Quintas-Cardama Alfonso, Verstovsek Srdan, Freireich Emil, Kantarjian Hagop, Chen Wen Yi and Zingaro Ralph, Chemical and Clinical Development of Darinaparsin, a Novel Organic Arsenic Derivative, Anti-Cancer Agents in Medicinal Chemistry 2008; 8 (8) . https://dx.doi.org/10.2174/187152008786847666
DOI https://dx.doi.org/10.2174/187152008786847666 |
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
-
Chemotherapy and Target Therapy in the Management of Adult High- Grade Gliomas
Current Cancer Drug Targets Marine Peptides and Related Compounds in Clinical Trial+
Anti-Cancer Agents in Medicinal Chemistry HDAC Inhibitors as Novel Anti-Cancer Therapeutics
Recent Patents on Anti-Cancer Drug Discovery Use of Analogs of Peptide Hormones Conjugated to Cytotoxic Radicals for Chemotherapy Targeted to Receptors on Tumors
Current Drug Delivery Bone Target Radiotracers for Palliative Therapy of Bone Metastases
Current Medicinal Chemistry Organophosphorus Chemistry: Therapeutic Intervention in Mechanisms of Viral and Cellular Replication
Current Organic Chemistry Pulmonary Infections in the Era of Biological Agents
Current Respiratory Medicine Reviews Serum miRNAs Signature Plays an Important Role in Keloid Disease
Current Molecular Medicine Polyphenols: Biological Activities, Molecular Targets, and the Effect of Methylation
Current Molecular Pharmacology Inhibitors of the PI3K/Akt/mTOR Pathway: New Hope for Breast Cancer Patients
Recent Patents on Anti-Cancer Drug Discovery Treatment for Cancer Patients with Oral Mucositis: Assessment Based on the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer in International Society of Oral Oncology (MASCC/ISOO) in 2013 and Proposal of Possible Novel Treatment with a Japanese Herbal Medicine
Current Pharmaceutical Design Recent Advances in the Therapeutic Perspectives of Nutlin-3
Current Pharmaceutical Design Comparision of Clinical Findings with CTPA Findings in Pulmonary Embolism
Current Medical Imaging Advances in Nanomaterials for Diagnosis and Therapy of Leukemia
Recent Patents on Nanomedicine Experimental Animal Models of Myocardial Damage in Regenerative Medicine Studies Involving Adult Bone Marrow Derived Stem Cells: Ethical and Methodological Implications
Cardiovascular & Hematological Disorders-Drug Targets EGFR(s) in Aging and Carcinogenesis of the Gastrointestinal Tract
Current Protein & Peptide Science Transcriptome and Proteome Analyses of Drug Interactions with Natural Products
Current Drug Metabolism Yin and Yang of Polyphenols in Cancer Prevention: A Short Review
Anti-Cancer Agents in Medicinal Chemistry Treatment of Central Nervous System Tuberculosis Infections and Neurological Complications of Tuberculosis Treatment
Current Pharmaceutical Design Chromatin Remodeling Agents for Cancer Therapy
Reviews on Recent Clinical Trials