957345-85-6Relevant articles and documents
METHODS OF TREATING NEURODEGENERATIVE DISEASES
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, (2020/03/23)
Described herein are methods of treating or preventing an ASK1 or DYRK1A associated disease, disorder, or condition comprising administering to a subject in need thereof a dual inhibitor of ASK1 and DYRK1A; including administering pharmaceutically acceptable salts and solvates thereof.
Discovery and Optimization of Quinazolinone-pyrrolopyrrolones as Potent and Orally Bioavailable Pan-Pim Kinase Inhibitors
Pettus, Liping H.,Andrews, Kristin L.,Booker, Shon K.,Chen, Jie,Cee, Victor J.,Chavez, Frank,Chen, Yuping,Eastwood, Heather,Guerrero, Nadia,Herberich, Bradley,Hickman, Dean,Lanman, Brian A.,Laszlo, Jimmy,Lee, Matthew R.,Lipford, J. Russell,Mattson, Bethany,Mohr, Christopher,Nguyen, Yen,Norman, Mark H.,Powers, David,Reed, Anthony B.,Rex, Karen,Sastri, Christine,Tamayo, Nuria,Wang, Paul,Winston, Jeffrey T.,Wu, Bin,Wu, Tian,Wurz, Ryan P.,Xu, Yang,Zhou, Yihong,Tasker, Andrew S.,Wang, Hui-Ling
, p. 6407 - 6430 (2016/07/26)
The high expression of proviral insertion site of Moloney murine leukemia virus kinases (Pim-1, -2, and -3) in cancers, particularly the hematopoietic malignancies, is believed to play a role in promoting cell survival and proliferation while suppressing apoptosis. The three isoforms of Pim protein appear largely redundant in their oncogenic functions. Thus, a pan-Pim kinase inhibitor is highly desirable. However, cell active pan-Pim inhibitors have proven difficult to develop because Pim-2 has a low Km for ATP and therefore requires a very potent inhibitor to effectively block the kinase activity at cellular ATP concentrations. Herein, we report a series of quinazolinone-pyrrolopyrrolones as potent and selective pan-Pim inhibitors. In particular, compound 17 is orally efficacious in a mouse xenograft model (KMS-12 BM) of multiple myeloma, with 93% tumor growth inhibition at 50 mg/kg QD upon oral dosing.
BIARYL COMPOUNDS USEFUL FOR THE TREATMENT OF HUMAN DISEASES IN ONCOLOGY, NEUROLOGY AND IMMUNOLOGY
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Paragraph 0166, (2015/06/25)
The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
