Target nature :
haspin
CAS n° :
2787548-37-0
Mecanism of action :
ATP-competitive inhibitor; IC50 Haspin: 6 nM
Physico-chemical properties :
Solubility in DMSO (10 mM)
solubilité en milieu biologie à préciser à 25 micro M
Molecular Weight: 350,38
Probe availability :
Chimiothèque ICOA (reference locale 53409571, adresser la demande à laurent.robin@univ-orleans.fr )
Princeps reference :
Journal of Enzyme Inhibition and Medicinal Chemistry. 2020, (35) 1: 1840-53. https://doi.org/10.1080/14756366.2020.1825408
More bibliography :
Other available information on the probe :
(S)-2-(((3-(1H-indazol-5-yl)imidazo[1,2-b]pyridazin-6-yl)oxy)methyl)morpholine
Other information on the target :
Haspin protein kinase has essential functions in mitosis. Its inhibition or depletion leads to severe mitotic defects leading to cell death by mitotic catastrophe. Haspine phosphorylates Histone H3 on Threonine 3 at the beginning of mitosis and this phosphorylated residue serves as an anchoring site for the Aurora B kinase complex (CPC), leading to its accumulation and activation at the centromere by a positive feedback loop. The centromeric localization of Aurora B is essential for the maintenance of chromosomal stability. Haspin has been found to be overexpressed in several highly proliferative malignancies and this overexpression often correlates with the most aggressive stages of the cancers.
Selectivity profile :
ATP-competitive inhibitor; IC50 Haspin: 6 nM; IC50 Aurora B > 10 µM; IC50 CDK1/CycB1: 2.3 µM; IC50 CDK2/CycA: 4.3 µM; IC50 CDK5/p25: 0.9 µM; IC50 CDK9/CycE: 170 nM; IC50 DYRK1A: 300 nM; IC50 GSK3: 360 nM; IC50 PIM1: 3.3 µM, IC50 PLK1 > 10 µM.
In vivo data :
not determined
In vitro data :
IC50 Haspin: 6 nM; 85% inhibition of endogenous Haspin activity at 50 nM (U-2 OS cells). Shown to effectively block cells in G2/M phase as well as affecting G1/S transition. Cell viability tested at 48h: EC50 on U-2 OS (osteosarcoma): 2.8 µM; EC50 on RPE1 (hTERT-immortalized retinal pigment epithelial cells): 4.6 µM. Shown to effectively affect U-2 OS spheroids growth at 5 µM.
Toxicity :
not evaluated in vivo
Chaine SMILES :
c2cc1[nH]ncc1cc2c4cnc5ccc(OC[C@@H]3CNCCO3)nn45
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