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Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors
Amr K A Bass1, Mona S El-Zoghbi1, El-Shimaa M Nageeb2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt.
Abstract:
Despite the encouraging clinical progress of chemotherapeutic agents in cancer treatment, innovation and development of new effective anticancer candidates still represents a challenging endeavor. With 15 million death every year in 2030 according to the estimates, cancer has increased rising of an alarm as a real crisis for public health and health systems worldwide. Therefore, scientist began to introduce innovative solutions to control the cancer global health problem. One of the promising strategies in this issue is the multitarget or smart hybrids having two or more pharmacophores targeting cancer. These rationalized hybrid molecules have gained great interests in cancer treatment as they are capable to simultaneously inhibit more than cancer pathway or target without drug-drug interactions and with less side effects. A prime important example of these hybrids, the HDAC hybrid inhibitors or referred as multitargeting HDAC inhibitors. The ability of HDAC inhibitors to synergistically improve the efficacy of other anti-cancer drugs and moreover, the ease of HDAC inhibitors cap group modification prompt many medicinal chemists to innovate and develop new generation of HDAC hybrid inhibitors. Notably, and during this short period, there are four HDAC inhibitor hybrids have entered different phases of clinical trials for treatment of different types of blood and solid tumors, namely; CUDC-101, CUDC-907, Tinostamustine, and Domatinostat. This review shed light on the most recent hybrids of HDACIs with one or more other cancer target pharmacophore. The designed multitarget hybrids include topoisomerase inhibitors, kinase inhibitors, nitric oxide releasers, antiandrogens, FLT3 and JAC-2 inhibitors, PDE5-inhibitors, NAMPT-inhibitors, Protease inhibitors, BRD4-inhibitors and other targets. This review may help researchers in development and discovery of new horizons in cancer treatment.
Insights
Developing novel anticancer agents is crucial due to rising cancer deaths. Multitargeting hybrids, especially HDAC inhibitors, offer a promising strategy by simultaneously targeting multiple cancer pathways with fewer side effects.
Area of Science:
- Oncology
- Medicinal Chemistry
- Drug Discovery
Background:
- Cancer remains a global health crisis, necessitating innovative therapeutic strategies beyond traditional chemotherapeutics.
- Multitargeting hybrid molecules, which combine multiple pharmacophores, are emerging as a promising approach to overcome treatment challenges and reduce side effects.
- Histone deacetylase (HDAC) inhibitors, a class of multitargeting agents, show potential for synergistic effects with other anticancer drugs and offer facile modification for new drug development.
Purpose of the Study:
- To review recent advancements in multitargeting HDAC inhibitor hybrids for cancer treatment.
- To highlight novel hybrid molecules combining HDAC inhibition with other cancer-targeting pharmacophores.
- To provide insights for future research and development in the discovery of new anticancer therapies.
Main Methods:
- Literature review of recent scientific publications and clinical trial data.
- Analysis of designed multitargeting HDAC inhibitor hybrids and their targeted pathways.
- Identification of key examples of HDAC inhibitor hybrids currently in clinical trials.
Main Results:
- Several HDAC inhibitor hybrids have advanced to clinical trials for various blood and solid tumors, including CUDC-101, CUDC-907, Tinostamustine, and Domatinostat.
- The reviewed multitargeting hybrids incorporate diverse pharmacophores, such as topoisomerase inhibitors, kinase inhibitors, and nitric oxide releasers.
- These hybrids are designed to simultaneously inhibit multiple cancer-related pathways, offering a rationalized approach to treatment.
Conclusions:
- Multitargeting HDAC inhibitor hybrids represent a significant advancement in cancer therapy.
- The development of these rationalized hybrid molecules holds promise for improved efficacy and reduced toxicity.
- This review provides a foundation for further exploration and discovery of novel anticancer agents in this class.
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