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Structure-activity relationship of 7-aryl-2-anilino-pyrrolopyrimidines as Mer and Axl tyrosine kinase inhibitors.

ABSTRACT: The TAM (Axl, Mer, and Tyro3) family is implicated in the survival and chemoresistance of tumours and has emerged as a potential therapeutic target. A novel series of 7-aryl-2-anilino-pyrrolopyrimidines were identified as potent Axl/Mer tyrosine kinase inhibitors without significant inhibition of Tyro3. A representative compound 27 exhibited IC₅₀ values of 2 nM and 16 nM for Mer and Axl, respectively, and considerable inhibition for Mer phosphorylation in cells. Docking studies suggested that the formation of a salt bridge between the nitrogen of the aniline moiety with ASP678 of the Mer kinase domain as well as an interaction with the hinge region that most kinase inhibitors have in common would be essential to retain activity. These results could provide useful information for finding promising inhibitors of Axl/Mer for the treatment of cancer.

SUBMITTER: Chung SH

PROVIDER: S-EPMC7534383 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Structure-activity relationship of 7-aryl-2-anilino-pyrrolopyrimidines as Mer and Axl tyrosine kinase inhibitors.

Chung Shin Hyuck SH Park Jiwon J Lee Jung Wuk JW Song Jiho J Jung Danbee D Min Kyung Hoon KH

Journal of enzyme inhibition and medicinal chemistry 20201201 1

The TAM (Axl, Mer, and Tyro3) family is implicated in the survival and chemoresistance of tumours and has emerged as a potential therapeutic target. A novel series of 7-aryl-2-anilino-pyrrolopyrimidines were identified as potent Axl/Mer tyrosine kinase inhibitors without significant inhibition of Tyro3. A representative compound <b>27</b> exhibited IC<sub>50</sub> values of 2 nM and 16 nM for Mer and Axl, respectively, and considerable inhibition for Mer phosphorylation in cells. Docking studies ...[more]

PMID: 32972253

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