2023年6月3日 · In this paper, we will showcase a series of anthranilic acid-derived inhibitors that bind an allosteric pocket of cyclin-dependent kinase 2 (CDK2) with nanomolar affinity. CDK2 is a member of...

2015年9月17日 · We describe the first example of an irreversible inhibitor that targets CDK2 by grafting a reactive vinyl sulfone moiety onto a potent reversible CDK2 inhibitor. The structure of the CDK2/cyclin A/NU6300 complex reveals the inhibitor binding mode within the ATP binding site and confirms that the vinyl sulfone forms a covalent bond to the ε ...

2022年5月20日 · Cyclin-dependent kinase 2 (CDK2) complex is significantly over-activated in many cancers. While it makes CDK2 an attractive target for cancer therapy, most inhibitors against CDK2...

In this paper, we will showcase a series of anthranilic acid-derived inhibitors that bind an allosteric pocket of cyclin-dependent kinase 2 (CDK2) with nanomolar afnity. fi CDK2 is a member...

Our data show that NU6140 binds to CDK2 with a Kd of 800 nM as determined by SPR and stabilizes the protein against thermal denaturation (ΔT m-5°C). The cocrystal structure determined in our study shows that NU6140 binds in the ATP-binding pocket as expected for this class of compounds and interacts with Leu83 and Glu81 with regular hydrogen ...

2019年1月17日 · We next employed surface plasmon resonance (SPR) as an orthogonal technique to measure inhibitor binding to cyclin-free CDK1 and CDK2 (Table 2). Glutathione-S-transferase (GST) fusions of CDK1 and CDK2 were immobilized on a chip coated with an anti-GST antibody and each inhibitor was flowed over as the analyte.

2022年6月30日 · showcase a series of anthranilic acid-derived inhibitors that bind an allosteric pocket of cyclin-dependent kinase 2 (CDK2) with nanomolar affinity. CDK2 is a member of the CDK family of kinases that control the cell cycle and is activated by binding E-type cyclins at the G1-S transition, then by A-type cyclins in S phase. Additionally,

Cyclin-dependent kinase 2 (CDK2) is a MITF target gene that is involved in regulating the cell cycle. CDK2 expression appears to be essential for melanoma clonogenic growth, and in a series of melanoma cell lines and human melanoma samples, MITF and CDK2 expression levels were found to be tightly correlated [57] .

2021年3月3日 · We describe reconstitution of stable complexes containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated by the CDK regulatory subunit CKS1. We further show that a direct interaction between a SKP2 N-terminal motif and cyclin A can stabilize SKP1-SKP2-CDK2-cyclin A complexes in the absence of CKS1.

Most inhibitors of Cyclin-dependent kinase 2 (CDK2) target its ATP-binding pocket. It is difficult, however, to use this pocket to design very specific inhibitors because this catalytic pocket...