Characterization of SPK 98, a Torin2 analog, as ATR and mTOR dual kinase inhibitor.

Characterization of SPK 98, a Torin2 analog, as ATR and mTOR dual kinase inhibitor. Bioorg Med Chem Lett. 2020 Sep 07;:127517 Authors: Bhakuni R, Shaik A, Priya B, Kirubakaran S Abstract A series of Torin2, a second-generation ATP-competitive inhibitor, analogues were biologically characterized to identify their potential for ATR and mTOR kinase inhibition. Compound SPK 98 was observed to inhibit ATR/mTOR kinase selectively over ATM kinase in HCT116 cell line. In addition to that, SPK 98 on 30 min incubation with human, mice and rat liver microsomes showed improved properties with an increased half-life (a maximum T ½ of 157 min) and internal clearance in mouse as compared to Torin2. Further, SPK 98 was also noticed to indulge in inducing premature chromatin condensation as a result of ATR/mTOR kinase inhibition at 50nM. In a nutshell, our work presents the identification and characterization, SPK 98 a small molecule inhibitor which exhibits improved specific inhibition for ATR at a lower concentration than Torin2. PMID: 32911078 [PubMed - as supplied by publisher]
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Tags: Bioorg Med Chem Lett Source Type: research