NU6027 is a potent ATR/CDK inhibitor, inhibits CDK1/2, ATR andDNA-PK with Ki of 2.5 μM/1.3 μM, 0.4 μM and 2.2 μM, enter cells more readily than the 6-aminopurine-based inhibitors.
Cyclin-dependent kinases (CDKs) are the catalytic subunits of a family of mammalian heterodimeric serine/threonine kinases that have been implicated in the control of cell-cycle progression, transcription and neuronal function[3].
NU6027 is a potent and ATP-competitive inhibitor of both CDK1 and CDK2, with Kis of 2.5 µM and 1.3 µM, respectively. NU6027 is also a potent inhibitor of ATR and enhances hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner[4]. NU6027 attenuated G2/M arrest following DNA damage, inhibited RAD51 focus formation and increased the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy but not the antimitotic, paclitaxel. NU6027 was synthetically lethal when DNA single-strand break repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition or defects in XRCC1[5]. NU6027 prevented the Trovafloxacin-mediated increases in LPS-induced TNF mRNA and protein release, Trovafloxacin prolonged TNF mRNA stability, and this effect was largely attenuated by NU6027[6]. NU-6027 inhibits Mycobacterium bovis BCG growth in vitro and also displayed cross-reactivity with Mycobacterium tuberculosis protein kinase D (PknD) and protein kinase G (PknG)[7].
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