1323981-23-2Relevant 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.
, p. 8989 - 9002 (2017)
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 0255, (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.
PHARMACOLOGICALLY ACTIVE COMPOUNDS
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Paragraph 00360, (2014/03/26)
The present invention relates to compounds of formula (II) wherein X, Y, R2, R3, R4 and Ar are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.
