1192755-07-9Relevant academic research and scientific papers
Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay
Rohe, Alexander,Goellner, Christiane,Wichapong, Kanin,Erdmann, Frank,Al-Mazaideh, Ghassab M.A.,Sippl, Wolfgang,Schmidt, Matthias
, p. 41 - 48 (2013/04/23)
In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay. These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full-length Myt1 expressed in a human cell line. Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect. We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase. The glycoglycerolipids showed no significant effects in the binding assay, endorsing the idea of a mechanism of action distant from the active site.
Synthesis of glycoglycerolipid of 1,2-dipalmitoyl-3-(N-palmitoyl-6′- amino-6′-deoxy-α-D-glucosyl)-sn-glycerol and its analogues, inhibitors of human Myt1-kinase
Sun, Yihua,Zhang, Jun,Li, Chunxia,Guan, Huashi,Yu, Guangli
, p. 6 - 12 (2012/08/08)
A glycoglycerolipid 1a isolated from a marine alga showed inhibition to Myt1 kinase with IC50 of 0.12 μg/mL. We synthesized 1a and its seven analogues (1b-h) in an efficient method with high stereoselectivity. The process employed trichloroacetimidate donor 4b at low substrate concentration to achieve high α-selectivity (α/β = 33:1) in glycosylation reaction. The present synthesis provided various acyl derivatives required for the study on the structure-activity relationship later.
First total synthesis of 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol-a glycoglycerolipid of a marine alga with a high inhibitor activity against human Myt1-kinase
Goellner, Christiane,Philipp, Claudia,Dobner, Bodo,Sippl, Wolfgang,Schmidt, Matthias
experimental part, p. 1628 - 1631 (2009/12/09)
The first total synthesis of 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol, a glycoglycerolipid isolated from a marine alga extract, is described. Starting from α-methylglucopyranoside the multistep strategy allows the stereoselective synthesis of the final compound using various protective group procedures as well as derivatization of partial molecule domains. The latter offers the development of lead structures for inhibitors of human Myt1-kinase.
