1068149-52-9Relevant academic research and scientific papers
The discovery of small molecule chemical probes of Bcl-XL and Mcl-1
Prakesch, Michael,Denisov, Alexey Yu,Naim, Marwen,Gehring, Kalle,Arya, Prabhat
, p. 7443 - 7449 (2008)
A tetrahydroaminoquinoline-based library was generated with the goals of finding small molecule modulators of protein-protein interactions. Several library members as well as other related intermediates were tested for their ability to bind to Bcl-XL and Mcl-1 by in silico and 15N NMR studies. The NMR study led to the identification of the tetrahydroaminoquinoline-based nude scaffold, 7 as a weak binder (Kd = 200 μM for Bcl-XL and Kd = 300 μM for Mcl-1) to both proteins. Using this scaffold as the starting material, we then synthesized a focused library of only 9 derivatives by applying the principles of a fragment-based approach. All these derivatives were then tested by NMR and this led to the discovery of a novel, small molecule (MIPRALDEN, 17) as a binder to Mcl-1 and Bcl-XL (KD = 25 and 70 μM). This finding is novel because to our knowledge there are not many small molecules known in the literature that bind to Mcl-1. Crown Copyright
