- Structure-activity relationship of spop inhibitors against kidney cancer
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Speckle-type POZ protein (SPOP) is overexpressed in the nucleus and misallocated in the cytoplasm in almost all the clear-cell renal cell carcinomas (ccRCCs), which leads to kidney tumorigenesis. Previously, we elucidated that the oncogenic SPOP-signaling pathway in ccRCC could be suppressed by 6b that inhibits SPOP-mediated protein interactions. Herein, we have established a structure-activity relationship for 6b analogues as SPOP inhibitors. Compound 6lc suppresses the viability and inhibits the colony formation of ccRCC cell lines driven by cytoplasmic SPOP, superior to 6b. Compound 6lc binds to the SPOP protein in vitro and disrupts SPOP binding to phosphatase-and-tensin homologue (PTEN) in HEK293T cells, which causes the observable phenomena: a decline in the ubiquitination of PTEN, elevated levels of both PTEN and dual-specificity phosphatase 7, and decreased levels of phosphorylated AKT and ERK when ccRCC cell lines are exposed to 6lc in a dose-response manner. Taken together, compound 6lc is a potent candidate against kidney tumorigenesis.
- Dong, Ze,Wang, Zhen,Guo, Zhong-Qiang,Gong, Shouzhe,Zhang, Tao,Liu, Jiang,Luo, Cheng,Jiang, Hualiang,Yang, Cai-Guang
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p. 4849 - 4866
(2020/06/08)
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- X-ray Structure and Molecular Docking Guided Discovery of Novel Chitinase Inhibitors with a Scaffold of Dipyridopyrimidine-3-carboxamide
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Chitinases are the glycosyl hydrolase for catalyzing the degradation of chitin and play an indispensable role in bacterial pathogenesis, fungal cell wall remodeling, and insect molting. Thus, chitinases are attractive targets for therapeutic drugs and pes
- Yuan, Pengtao,Jiang, Xi,Wang, Siyu,Shao, Xusheng,Yang, Qing,Qian, Xuhong
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p. 13584 - 13593
(2020/12/02)
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- Characterization and structure-activity relationship study of iminodipyridinopyrimidines as novel hepatitis C virus inhibitor
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Upon high-throughput screening of synthetic small molecule libraries with the infectious hepatitis C virus (HCV) cell culture system, we identified an iminodipyridinopyrimidine (IDPP) scaffold. IDPP did not inhibit HCV replication, but exhibited very potent inhibitory activity on early and late steps of HCV life cycle. Applying an intensive structure-activity relationship (SAR) study, a promising IDPP Lead compound (12c) with excellent potency (EC50 = 10 nM), high safety margin (SI > 2000), and an acceptable stability in human and rat liver microsomes (t1/2 >60 min) was identified. Overall, our results suggest that the IDPP scaffold could be used for the development of novel HCV interventions.
- Park, Dong-Sik,Jo, Eunji,Choi, Jihyun,Lee, MyungEun,Kim, Soohyun,Kim, Hee-Young,Nam, Jiyon,Ahn, Sujin,Hwang, Jong Yeon,Windisch, Marc Peter
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- 2-imine-5-keto-2,5-dihydro-1-H-dipyridylpyrimidine compound
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The invention provides synthesis and purpose of a 2-imine-5-keto-2,5-dihydro-1-H-dipyrido [3,4-C: 1 ', 2'-F] pyrimidine compound. Specifically, the invention discloses a compound shown as a following general formula (I) and pharmaceutically-acceptable salt or a pharmaceutically-acceptable solvate, and the definitions of various genes are shown in the Specification. The compound can be taken as an inhibitor taking SPOP as a target or prepared into a drug for treating and/or preventing a disease (such as a kidney cancer and the like) taking the SPOP as the target.
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Paragraph 0105; 0106
(2017/10/25)
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- PYRIDMIDONES FOR TREATMENT OF POTASSIUM CHANNEL RELATED DISEASES
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The present invention relates to compounds of Formula I as described herein or a 1 pharmaceutically acceptable salt thereof, pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof and methods of treating, or manufacture of a medicament to treat, a disease, disorder, or condition of the central nervous system, including bipolar disorder, depressive disorders, anxiety disorders, cognitive disorders, pain disorders, urogenital disorders, and epilepsy, among the other diseases, disorders or conditions discussed herein as mono-therapy or in combination with another active pharmaceutical ingredient.
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Page/Page column 29
(2012/04/10)
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- ANTI - INFECTIVE PYRIDO (1,2 -A) PYRIMIDINES
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The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
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Page/Page column 78; 81
(2011/08/04)
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- Anti-infective compounds
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The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
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Page/Page column 36, 37
(2011/08/04)
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