LDN-192960 2HCl

LDN-192960 is a potent Haspin (Haploid Germ Cell-Specific Nuclear Protein Kinase) inhibitor with an IC50 of 0.010 µM.

Signaling Pathways >> Cell Cycle/DNA Damage >> Haspin Kinase

Research Areas >> Cancer

IC50: 0.010 μM (Haspin)[1]

A comparison of the profiles of LDN-192960 (compound 3) and 42 suggests that only six kinases, including haspin, are inhibited by both compounds ≥90% at 10 µM[1]. LDN-192960 alone does not cause detectable mitotic exit in the mitotic (phospho)-protein monoclonal-2 (MPM-2) assay in HeLa cells. In the presence of 1 µM ZM447439, even concentrations as low as 0.1 µM LDN-192960 cause substantial loss of MPM-2 epitopes, and similar results are obtained in the presence of Hesperadin. However, 10 µM LDN-192960 does not cause mitotic exit in combination with Aurora B inhibition, which is consistent with off-target effects at this higher dose[2].

U2OS cells and H2B-mRFP are used. For imaging, mitotic cells arrested in 5 µM nocodazole for ~8 h are harvested by “shake-off” and replated in 10% FBS, 25 mM Hepes, and phenol red-free DME containing 5 µM nocodazole in a 35-mm single chamber or 35-mm 4-chamber glass-bottom dishes coated with poly-d-lysine. Time-lapse confocal fluorescence imaging is performed using an inverted microscope. Immediately after kinase inhibitor (including LDN-192960) addition, two-color z stacks with 0.8 µm steps are collected with a 100-nm pinhole every 5 min for 15 h[2].

[1]. Cuny GD, et al. Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors. Bioorg Med Chem Lett. 2012 Mar 1;22(5):2015-9.

[2]. Fangwei Wang, et al. Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. J Cell Biol. 2012 Oct 15; 199(2): 251-268.

CHR-6494