The phosphorylation of CHK1 at Ser345 regulates the phenotypic switching of vascular smooth muscle cells both in vitro and in vivo

4 views | Dec 25 2020

Chen Xin et al. demonstrated that phosphorylation of CHK1 under DNA damage stress modulated VSMCs phenotypic switching. [Read the Full Post]

Crystal Structure of the Kinase Domain of MerTK in Complex with AZD7762 Provides Clues for Structure-Based Drug Development

6 views | Dec 23 2020

Tae Hyun Park et al. determined the crystal structure of the MerTK:AZD7762 complex and revealed the binding mode of AZD7762 to MerTK. [Read the Full Post]

Resistance to the CHK1 inhibitor prexasertib involves functionally distinct CHK1 activities in BRCA wild-type ovarian cancer

10 views | Nov 29 2020

Jayakumar Nair et al. demonstrated new mechanistic insights of functionally distinct CHK1 activities and highlighted a potential combination treatment approach to overcome CHK1i resistance in BRCAwt HGSOC. [Read the Full Post]

Phosphoproteomics Analysis Reveals a Potential Role of CHK1 in Regulation of Innate Immunity through IRF3

16 views | Nov 09 2020

Zhen Chen et al. indicated that the CHK1-dependent regulation of IRF3 phosphorylation at S173 and S175 might play a role in the induction of innate immune response after replication stress or DNA damage, which suggested a potential function of CHK1 in the innate immune response. [Read the Full Post]

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

15 views | Nov 09 2020

Stanislav Drápela et al. suggested that metabolically robust and selective CHK1 inhibitor MU380 could bypass docetaxel resistance and improve the effectiveness of GEM in DR mCRPC models. [Read the Full Post]

Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells

19 views | Oct 16 2020

Svenja Wiechmann et al.improved the understanding of radioresistance and provided avenues for developing radiotherapeutic strategies. [Read the Full Post]

A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients

99 views | Apr 13 2020

Laquente B et al. showed that LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer. [Read the Full Post]

Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling

96 views | Apr 12 2020

Wang L et al. indicated that in addition to acting as a tumor suppressor, AZD7762 may prevent bone loss by inhibiting osteoclastogenesis and stimulating osteoblast mineralization. [Read the Full Post]

CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib

103 views | Apr 07 2020

Sen T et al. provided a preclinical proof of concept supporting the initiation of a clinical efficacy trial in patients with platinum-sensitive or platinum-resistant relapsed SCLC. [Read the Full Post]

Prexasertib treatment induces homologous recombination deficiency and synergizes with olaparib in triple-negative breast cancer cells

109 views | Apr 07 2020

Mani C et al. indicted that RAD51 could be a biomarker for aggressive TNBC and for racial disparity in breast cancer. As positive correlation exists between RAD51 and CHEK1 expression in breast cancer, the in vitro preclinical data presented here provides additional mechanistic insights for further evaluation of the rational combination of prexasertib and olaparib for improved outcomes and reduced racial disparity in TNBC. [Read the Full Post]