Current Inhibitors of Checkpoint Kinase 2

Nguyen, Thu Nhan; Tepe, Jetze J.

doi:10.2174/092986711797200390

Cited by 6 publications

(6 citation statements)

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“…The different peaks at 2θ = 38, 44 and 64° in the XRD pattern of the CHN were assigned to Ag nanoparticles incorporated in the nanocomposite network. These peaks correspond to scattering from the (111), (211), and (220) planes, respectively . Thus, the obtained result further demonstrates AgNPs were successfully fabricated in this work.…”

Section: Resultssupporting

confidence: 67%

Synthesis of poly(AN)/poly(AA‐co‐AM) hydrogel nanocomposite with electrical conductivity and antibacterial properties

Hosseinzadeh

Barghi

2018

Polymer Composites

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In this study, a novel conductive hydrogel nanocomposite (CHN) was prepared using chemical oxidative polymerization of aniline (AN), acrylic acid (AA), and acrylamide (AM) and subsequent in situ synthesis of silver nanoparticles. The structure of CHNs was characterized by Fourier transform infrared, scanning electron microscopy, Transmission electron microscopy, EDX, X‐ray diffraction, and UV‐Vis analysis techniques and a proposed mechanism for the preparation of CHNs was also suggested. The maximum water‐swelling capacity (78 g g−1) was achieved under the optimum conditions that found to be: AA = 0.2 mol L−1, AM = 0.18 mol L−1, AN = 0.1 mol L−1, swelling time = 180 min, and temperature = 25°C. In addition, the effect of reaction parameters were studied with respect to the percent of impregnated poly(AN) within nanocomposites. Further, the electrical conductivity of CHN samples was found to be increased with the increase in AN content and temperature whose conductivity lies in the range 2.1 to 8.8 × 103 S cm−1. The temperature dependence of electrical conductivity indicates that composites follow Arrhenius model. Moreover, the synthesized CHNs demonstrated an antibacterial action against Gram‐negative Escherichia coli bacterium. In conclusion, durable antibacterial and electrically conductive CHNs can be suitable for different types of applications in many fields i.e. in biological systems, wound dressing, catalysis, water purification, and flexible electrodes for supercapacitors. POLYM. COMPOS., 40:2724–2733, 2019. © 2018 Society of Plastics Engineers

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Section: Resultssupporting

confidence: 67%

Synthesis of poly(AN)/poly(AA‐co‐AM) hydrogel nanocomposite with electrical conductivity and antibacterial properties

Hosseinzadeh

Barghi

2018

Polymer Composites

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“…34 As a downstream kinase of ATM, CHK2 is a logical target for the development of radio-or chemosensitizers. Therefore, several small-sized inhibitors 35 have been proposed to precisely decipher its role in cell cycle arrest and tumourigenesis, and ultimately to validate its relevance as a target in oncology. Nevertheless, the advantage of using a dual CHK1/CHK2 inhibition over a CHK2 selective inhibition remains to be evaluated; thus, specific CHK2 inhibitors are under development.…”

Section: Checkpoint Kinase 1 (Chk1)mentioning

confidence: 99%

ATM, ATR, CHK1, CHK2 and WEE1 inhibitors in cancer and cancer stem cells

et al. 2017

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DNA inevitably undergoes a high number of damages throughout the cell cycle. To preserve the integrity of the genome, cells have developed a complex enzymatic machinery aimed at sensing and repairing DNA lesions, pausing the cell cycle to provide more time to repair, or induce apoptosis if damages are too severe. This so-called DNA-damage response (DDR) is yet considered as a major source of resistance to DNA-damaging treatments in oncology. Recently, it has been hypothesized that cancer stem cells (CSC), a sub-population of cancer cells particularly resistant and with tumour-initiating ability, allow tumour re-growth and cancer relapse. Therefore, DDR appears as a relevant target to sensitize cancer cells and cancer stem cells to classical radio- and chemotherapies as well as to overcome resistances. Moreover, the concept of synthetic lethality could be particularly efficiently exploited in DDR. Five kinases play pivotal roles in the DDR: ATM, ATR, CHK1, CHK2 and WEE1. Herein, we review the drugs targeting these proteins and the inhibitors used in the specific case of CSC. We also suggest molecules that may be of interest for preclinical and clinical researchers studying checkpoint inhibition to sensitize cancer and cancer stem cells to DNA-damaging treatments.

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“…The research field of checkpoint kinase (CHK) inhibitors has seen several recent developments, including publications of early phase clinical trial data for inhibitors used in combination with classical cancer chemotherapies, and also the first preclinical demonstrations of single agent efficacy for checkpoint kinase 1 (CHK1) inhibitors in specific genetic backgrounds. Previous reviews have covered the clinical development of CHK inhibitors [1-4] and the new structural classes of small molecules that have emerged from preclinical discovery [5-8]. In this article we concentrate on recently published structure-based drug design (SBDD) strategies that have enabled hit compounds against CHK1 and CHK2 to be developed to potent, selective late stage lead compounds and clinical candidates, and on advances made in understanding the determinants of inhibitor selectivity.…”

Section: Introductionmentioning

confidence: 99%

Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies

Matthews

Jones

Collins

2013

Expert Opinion on Drug Discovery

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Protein-bound water molecules play key roles in structural features that can be targeted to gain high selectivity for either enzyme. The results of early phase clinical trials of checkpoint inhibitors have been mixed, but significant progress has been made in testing the combination of CHK1 inhibitors with genotoxic chemotherapy. Second-generation CHK1 inhibitors are likely to benefit from increased selectivity and oral bioavailability. While the optimum therapeutic context for CHK2 inhibition remains unclear, the emergence of single agent preclinical efficacy for CHK1 inhibitors in specific tumour types exhibiting constitutive replication stress represents exciting progress in exploring the therapeutic potential of these agents.

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Current Inhibitors of Checkpoint Kinase 2

Cited by 6 publications

References 0 publications

Synthesis of poly(AN)/poly(AA‐co‐AM) hydrogel nanocomposite with electrical conductivity and antibacterial properties

Synthesis of poly(AN)/poly(AA‐co‐AM) hydrogel nanocomposite with electrical conductivity and antibacterial properties

ATM, ATR, CHK1, CHK2 and WEE1 inhibitors in cancer and cancer stem cells

Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies

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