Obatoclax mesylate : pharmacology and potential for therapy of hematological neoplasms
| Autor: | Jamal Joudeh, David F. Claxton |
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| Rok vydání: | 2012 |
| Předmět: |
Indoles
Lymphoma medicine.medical_treatment Antineoplastic Agents Apoptosis Drug resistance Pharmacology Targeted therapy chemistry.chemical_compound Drug Delivery Systems medicine Humans Pharmacology (medical) Pyrroles Clinical Trials as Topic Leukemia business.industry General Medicine medicine.disease Clinical trial chemistry Drug development Proto-Oncogene Proteins c-bcl-2 Drug Resistance Neoplasm Pharmacodynamics Hematological neoplasm business Obatoclax |
| Zdroj: | Expert opinion on investigational drugs. 21(3) |
| ISSN: | 1744-7658 |
| Popis: | Augmentation and acceleration of apoptosis for cancer therapy are logical therapeutic strategies given the increasing body of data suggesting the dysregulation of control of cell death in many neoplasms. Apoptosis is particularly well studied in hematological neoplasms, thus these varied diseases present opportunities for pro-apoptotic drug development both as single agents and in combination with established therapies. Accordingly, several agents targeting function of anti-apoptotic Bcl-2 family members have entered clinical trials in the last decade and are discussed.The pan Bcl-2 family member BH3 domain mimetic obatoclax (GX15-070) is currently under clinical evaluation in solid tumors and hematological neoplasms. This agent offers the attractive property of uniformly inhibiting all of the anti-apoptotic members of the Bcl-2 protein family. Its chemistry and preclinical development and activity are reviewed. Pharmacology, pharmacodynamics, drug resistance and clinical use of this agent in leukemias and lymphomas are discussed. The prospects for obatoclax in changing clinical practice are addressed.Obatoclax may not prove to have dramatic single agent activity for hematological neoplasms. It seems more likely that its activity will be manifest in combination therapy with other agents, particularly cytotoxic chemotherapies. Results of ongoing studies are awaited. |
| Databáze: | OpenAIRE |
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