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ATM/ATR

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 views | Mar 30 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

Structure of the intact ATM/Tel1 kinase

9 views | Mar 16 2020

Wang X et al. provided a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents. [Read the Full Post]

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

7 views | Mar 16 2020

Tian X et al.demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 views | Feb 16 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

0 views | Jan 12 2020

Hendriks CMM et al. suggested that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. [Read the Full Post]

PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells

55 views | Jan 06 2020

Wang Y et al. revealed that LY294002 displays the opposite effect on PI3K-dependent AKT phosphorylation, which maintains cell survival from the cytotoxicity introduced by LY294002 itself in GEM-resistant pancreatic cancer cells. We suggest that targeting the PI3K/AKT signaling pathway with inhibitors may be counterproductive for patients with PC who have acquired GEM-resistance. [Read the Full Post]

Predictability, efficacy and safety of radiosensitization of glioblastoma-initiating cells by the ATM inhibitor KU-60019

41 views | Jan 05 2020

Vecchio D et al. suggested that GIC-driven tumors with low expression of TP53 and high expression of PI3K might be effectively and safely radiosensitized by KU-60019. [Read the Full Post]

The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia

56 views | Dec 24 2019

Deng L et al. indicated that the PI3K/mTOR dual inhibitor BEZ235 effectively chemosensitizes AML cells via increasing miR-1-3p and subsequently down-regulating BAG4, EDN1 and ABCB1. [Read the Full Post]

NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma

66 views | Dec 24 2019

Huang JC et al. suggested NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS. [Read the Full Post]

Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models

70 views | Dec 23 2019

Netland IA et al. suggested that despite the anti-neoplastic efficacy of dactolisib in glioma treatment in vitro, its utility in vivo is questionable due to toxicity. [Read the Full Post]