934744-50-0Relevant academic research and scientific papers
The Discovery of a Dual TTK Protein Kinase/CDC2-Like Kinase (CLK2) Inhibitor for the Treatment of Triple Negative Breast Cancer Initiated from a Phenotypic Screen
Riggs, Jennifer R.,Nagy, Mark,Elsner, Jan,Erdman, Paul,Cashion, Dan,Robinson, Dale,Harris, Roy,Huang, Dehua,Tehrani, Lida,Deyanat-Yazdi, Gordafaried,Narla, Rama Krishna,Peng, Xiaohui,Tran, Tam,Barnes, Leo,Miller, Terra,Katz, Jason,Tang, Yang,Chen, Ming,Moghaddam, Mehran F.,Bahmanyar, Sogole,Pagarigan, Barbra,Delker, Silvia,Lebrun, Laurie,Chamberlain, Philip P.,Calabrese, Andrew,Canan, Stacie S.,Leftheris, Katerina,Zhu, Dan,Boylan, John F.
supporting information, p. 8989 - 9002 (2017/11/14)
Triple negative breast cancer (TNBC) remains a serious unmet medical need with discouragingly high relapse rates. We report here the synthesis and structure-activity relationship (SAR) of a novel series of 2,4,5-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines with potent activity against TNBC tumor cell lines. These compounds were discovered from a TNBC phenotypic screen and possess a unique dual inhibition profile targeting TTK (mitotic exit) and CLK2 (mRNA splicing). Design and optimization, driven with a TNBC tumor cell assay, identified potent and selective compounds with favorable in vitro and in vivo activity profiles and good iv PK properties. This cell-based driven SAR produced compounds with strong single agent in vivo efficacy in multiple TNBC xenograft models without significant body weight loss. These data supported the nomination of CC-671 into IND-enabling studies as a single agent TNBC therapy.
SUBSTITUTED PYRROLOPYRIMIDINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Paragraph 0332, (2014/07/23)
Provided herein are Pyrrolopyrimidine Compounds having the following structure: wherein R1, R2, R3, and L are as defined herein, compositions comprising an effective amount of a Pyrrolopyrimidine Compound, and methods for treating or preventing breast cancer, more particularly triple negative breast cancer, comprising administering an effective amount of such Pyrrolopyrimidine Compounds to a subject in need thereof.
SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS
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, (2011/04/14)
Compounds of Formula I: and salts thereof in which R1, R2, R2a, R3, n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.
