Design, synthesis and biological evaluation of novel 4-arylaminopyrimidine derivatives possessing a hydrazone moiety as dual inhibitors of L1196M ALK and ROS1

Wang, Yu; Zhang, Guogang; Hu, Gang; Bu, Yanxin; Lei, Hongrui; Zuo, Daiying; Han, Meihua; Zhai, Xin; Gong, Ping

doi:10.1016/j.ejmech.2016.06.056

Cited by 23 publications

(8 citation statements)

References 22 publications

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“…When the ISO concentration is above 4 μg/mL, ZnO–ISO begins to exhibit strong cytotoxicity. It should be mentioned that our MTT results of ISO, Nintedanib, and Crizotinib are consistent with those previous reports. − …”

Section: Resultssupporting

confidence: 92%

Self-Assembled ZnO Nanoparticle Capsules for Carrying and Delivering Isotretinoin to Cancer Cells

Zhao

Wei

Zhang

et al. 2017

ACS Appl. Mater. Interfaces

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ZnO@polymer core-shell nanoparticles are assembled into novel capsule shells with diameters of about 100 nm to load isotretinoin (ISO) with a capacity as high as 34.6 wt %. Although ISO, a widely used drug for acne treatment, by itself is not suitable for treating cancer because of its hydrophobicity, our ZnO-ISO composite showed much stronger anticancer activity. The improved cytotoxicity is ascribed to the synergistic effects of the ZnO@polymer and ISO, where the ZnO@polymer helps in the accumulation of ISO in cancer cells on the one hand, and on the other hand, ISO is released completely through ZnO decomposition under acidic conditions of cancer cells. Such a pH-triggered drug-delivery system exhibits a much improved killing of cancer cells in vitro in comparison with the benchmarks, Nintedanib and Crizotinib, two commercial drugs clinically applied against lung cancer.

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Section: Resultssupporting

confidence: 92%

Self-Assembled ZnO Nanoparticle Capsules for Carrying and Delivering Isotretinoin to Cancer Cells

Zhao

Wei

Zhang

et al. 2017

ACS Appl. Mater. Interfaces

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“…b 'Inactive' means that kinase activity is inhibited by less than 50% even at 10 lM concentration of compound. c Activity value from the reference 15 .…”

Section: Antiproliferative Activities Of Selected Pyrazolo[34-b]pyrimentioning

confidence: 99%

“…ALK has received a great deal of attention as a promising therapeutic target for targeted cancer therapy and, as a result, enormous efforts have been devoted to developing ALK inhibitors. While various scaffolds such as pyrimidine, aminopyridine 8,9 , benzo[b]carbazolone 10 , indazole 11 have been exploited to identify new ALK inhibitors, 2,4-diarylamino pyrimidines 2,[12][13][14][15][16][17][18][19][20][21] have been the most common molecular platform for discovering ALK inhibitors including ceritinib and brigatinib. Crizotinib 22,23 was approved in 2011 as an ALK inhibitor for treatment of NSCLC patients harbouring EML4-ALK fusion oncogene.…”

Section: Introductionmentioning

confidence: 99%

Identification of 1H-pyrazolo[3,4-b]pyridine derivatives as potent ALK-L1196M inhibitors

Nam

Hwang

Kim³

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Anaplastic lymphoma kinase (ALK) has been recognised as a promising molecular target of targeted therapy for NSCLC. We performed SAR study of pyrazolo[3,4-b]pyridines to override crizotinib resistance caused by ALK-L1196M mutation and identified a novel and potent L1196M inhibitor, 10g. 10g displayed exceptional enzymatic activities (<0.5 nM of IC 50) against ALK-L1196M as well as against ALK-wt. In addition, 10g is an extremely potent inhibitor of ROS1 (<0.5 nM of IC 50) and displays excellent selectivity over c-Met. Moreover, 10g strongly suppresses proliferation of ALK-L1196M-Ba/F3 and H2228 cells harbouring EML4-ALK via apoptosis and the ALK signalling blockade. The results of molecular docking studies reveal that, in contrast to crizotinib, 10g engages in a favourable interaction with M1196 in the kinase domain of ALK-L1196M and hydrogen bonding with K1150 and E1210. This SAR study has provided a useful insight into the design of novel and potent inhibitors against ALK gatekeeper mutant.

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“…Due to these affirmative traits, hydrazones have been beneath study for a long time, however abundant of their basic chemistry remains unknown [4] . Hydrazones a division of organic compounds having the basic structure R1R2C=NNH2 [5,6] . They are joined to aldehydes and ketones, by the substitute of the chemical element with the -NNH2 cluster [7,8] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of new hydrazone

Parveen¹,

Kumar²

2020

Pharma Innovation

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Design, synthesis and biological evaluation of novel 4-arylaminopyrimidine derivatives possessing a hydrazone moiety as dual inhibitors of L1196M ALK and ROS1

Cited by 23 publications

References 22 publications

Self-Assembled ZnO Nanoparticle Capsules for Carrying and Delivering Isotretinoin to Cancer Cells

Self-Assembled ZnO Nanoparticle Capsules for Carrying and Delivering Isotretinoin to Cancer Cells

Identification of 1H-pyrazolo[3,4-b]pyridine derivatives as potent ALK-L1196M inhibitors

Synthesis and biological evaluation of new hydrazone

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