7312-14-3Relevant academic research and scientific papers
STAT DEGRADERS AND USES THEREOF
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Paragraph 00726; 00727, (2021/09/26)
The present invention provides compounds, compositions thereof, and methods of using the same.
SMALL MOLECULE STAT PROTEIN DEGRADERS
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Paragraph 0992, (2021/10/02)
The present disclosure provides compounds represented by Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R1a, R1b, R3a, R4, A, E1, E2, M, and Q are as set forth in the specification. Compounds of Formula (I) are STAT protein degraders and thus are useful for the treatment of cancer and other diseases.
Discovery of Novel Allosteric Inhibitors of Deoxyhypusine Synthase
Tanaka, Yuta,Kurasawa, Osamu,Yokota, Akihiro,Klein, Michael G.,Ono, Koji,Saito, Bunnai,Matsumoto, Shigemitsu,Okaniwa, Masanori,Ambrus-Aikelin, Geza,Morishita, Daisuke,Kitazawa, Satoshi,Uchiyama, Noriko,Ogawa, Kazumasa,Kimura, Hiromichi,Imamura, Shinichi
, p. 3215 - 3226 (2020/04/08)
Deoxyhypusine synthase (DHPS) utilizes spermidine and NAD as cofactors to incorporate a hypusine modification into the eukaryotic translation initiation factor 5A (eIF5A). Hypusine is essential for eIF5A activation, which, in turn, plays a key role in regulating protein translation of selected mRNA that are associated with the synthesis of oncoproteins, thereby enhancing tumor cell proliferation. Therefore, inhibition of DHPS is a promising therapeutic option for the treatment of cancer. To discover novel lead compounds that target DHPS, we conducted synthetic studies with a hit obtained via high-throughput screening. Optimization of the ring structures of the amide compound (2) led to bromobenzothiophene (11g) with potent inhibitory activity against DHPS. X-ray crystallographic analysis of 11g complexed with DHPS revealed a dramatic conformational change in DHPS, which suggests the presence of a novel allosteric site. These findings provide the basis for the development of novel therapy distinct from spermidine mimetic inhibitors.
STAT3 PROTEIN DEGRADERS
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Paragraph 0561, (2020/10/20)
The present disclosure provides compounds represented by Formulae I and IV: wherein R1a, R1b, R2a, R2b, A, E, QD, and QE are as defined in the specification, and the salts and solvates thereof. Compounds of Formula I are degraders of STAT3. Compounds of Formula IV are inhibitors of STAT3. STAT3 degraders and inhibitors are useful for the treatment of cancer and other diseases.
SMALL MOLECULE DEGRADERS OF STAT3
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Paragraph 1332, (2020/10/20)
The present disclosure provides compounds represented by Formula I or Formula VIII: wherein R1a, R1b, M, A, E, QA, and QB are as defined in the specification, and the salts and solvates thereof. Compounds of Formula I are degraders of STAT3 or dedraders of STAT3 and STAT1. Compounds of Formula VIII are inhibitors of STAT3. STAT3 degraders and inhibitors are useful for the treatment of cancer and other diseases.
STING AGONIST COMPOUNDS
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Paragraph 0718; 0719, (2019/10/23)
Compounds of general formula (I), of general formula (II), of general formula (III), of general formula (IV), of general formula (V), of general formula (VI), and their pharmaceutically acceptable salts, wherein all variables are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are compositions comprising such compounds, processes for the synthesis of such compounds, and to uses of such compounds, including administration of such compounds to induce immune response, to induce STING-dependent type I interferon production, and/or to treat a cell proliferation disorder, such as cancer.
