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

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dc.contributor.author Bhakuni, Rashmi
dc.contributor.author Shaik, Althaf
dc.contributor.author Priya, Bhanu
dc.contributor.author Kirubakaran, Sivapriya
dc.date.accessioned 2020-09-16T07:43:47Z
dc.date.available 2020-09-16T07:43:47Z
dc.date.issued 2020-09
dc.identifier.citation Bhakuni, Rashmi; Shaik, Althaf; Priya, Bhanu and Kirubakaran, Sivapriya, “Characterization of SPK 98, a Torin2 analog, as ATR and mTOR dual kinase inhibitor”, Bioorganic & Medicinal Chemistry Letters, DOI: 10.1016/j.bmcl.2020.127517, vol. 30, no. 23, Sep. 2020. en_US
dc.identifier.issn 0960-894X
dc.identifier.uri 10.1016/j.bmcl.2020.127517
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/5694
dc.description.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 � 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.
dc.description.statementofresponsibility by Rashmi Bhakuni, Althaf Shaik, Bhanu Priya and Sivapriya Kirubakaran
dc.language.iso en_US en_US
dc.publisher Elsevier en_US
dc.subject DNA damage response en_US
dc.subject ATR en_US
dc.subject ATM en_US
dc.subject cell cycle arrest en_US
dc.subject premature chromatin condensation en_US
dc.title Characterization of SPK 98, a Torin2 analog, as ATR and mTOR dual kinase inhibitor en_US
dc.type Article en_US
dc.relation.journal Bioorganic & Medicinal Chemistry Letters


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