- Structure-activity relationship of spop inhibitors against kidney cancer
-
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
-
p. 4849 - 4866
(2020/06/08)
-
- N-Arylalkylpiperidine urea derivatives as CC chemokine receptor-3 (CCR3) antagonists
-
The synthesis and structure-activity relationships of N- arylalkylpiperidylmethyl ureas as antagonists of the CC chemokine receptor-3 (CCR3) are presented. These compounds displayed potent binding to the receptor as well as functional antagonism of eotaxin-elicited effects on eosinophils.
- Batt, Douglas G.,Houghton, Gregory C.,Roderick, John,Santella III, Joseph B.,Wacker, Dean A.,Welch, Patricia K.,Orlovsky, Yevgeniya I.,Wadman, Eric A.,Trzaskos, James M.,Davies, Paul,Decicco, Carl P.,Carter, Percy H.
-
p. 787 - 791
(2007/10/03)
-
- Rapid microwave-assisted solution phase synthesis of substituted 2-pyridone libraries
-
2-Pyridone and 2-quinolone analogues are well-known biologically active heterocyclic scaffolds. Libraries of 3,5,6-substituted 2-pyridone derivatives are generated by rapid microwave assisted solution phase methods using a one-pot, two-step protocol. The three-component condensation of CH-acidic carbonyl compounds, N,N-dimethylformamide dimethylacetal and methylene active nitriles, leads to 2-pyridones and fused analogues in moderate to good overall yields and high purities. The proposed mechanism of this novel multi-component reaction, structure elucidation of products and intermediates are discussed.
- Gorobets, Nikolay Yu.,Yousefi, Behrooz H.,Belaj, Ferdinand,Kappe, C. Oliver
-
p. 8633 - 8644
(2007/10/03)
-
- N-substituted heterocyclic amines as modulators of chemokine receptor activity
-
The present application describes modulators of chemokine receptors of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
- -
-
Page/Page column 38
(2010/02/06)
-