Publications by authors named "Takenao Odagami"
The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the development of multiple types of cancer, and its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor of the interaction between β-catenin and CREB binding protein, which is part of the Wnt/β-catenin signaling pathway, disrupts the Wnt/β-catenin signaling pathway in HEK293 and adenomatous polyposis coli ()-mutated human gastric cancer ECC10 cells. It also inhibited tumor growth in an ECC10 xenograft model and suppressed polyp formation in the intestinal tract of mice, in which mutation of activates the Wnt/β-catenin signaling pathway.
View Article and Find Full Text PDFIn a previous Method Article, we have presented the 'Structure-Activity Relationship (SAR) Matrix' (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a "chemical space envelope" around related series.
View Article and Find Full Text PDFConformationally restricted peptidomimetics comprising eight stereoisomeric scaffolds with three-dimensional structural diversity were designed based on the structural features of cyclopropane, that is, cyclopropylic strain, which mimic wide-ranging tetrapeptide conformations covering β-turns through β-strands. Stereoselective synthesis of the designed peptidomimetics led to the identification of nonpeptidic melanocortin-4 receptor ligands.
View Article and Find Full Text PDFIdentification of new agonists of urotensin-II from a cyclic peptide library.
Bioorg Med Chem
September 2009
Article Synopsis
- Urotensin-II (UT-II) plays a role in regulating cardiovascular health and disease, prompting research into its receptor, GPR-14.
- A cyclic hexapeptide library based on the UT-II sequence led to the discovery of a new synthetic sequence (WK[Xaa]) that effectively activates the receptor, unlike the previously used WK[Y] sequence.
- Compound 1, identified in the study, exhibited strong agonistic activity with an EC(50) of 6.94 nM, while structural analysis revealed it lacked a typical secondary structure, paving the way for further exploration of UT-II's active conformation and new ligand discovery for GPR-14.
The deprotection of the indole (N(ind))-formyl (For) group on Trp was achieved in a 95% yield using N,N'-dimethylethylendiamine (DMEDA) (1.5, 2.0, 3.
View Article and Find Full Text PDFDesign of cyclic peptides with agonist activity at melanocortin receptor-4.
Bioorg Med Chem Lett
July 2006
Article Synopsis
- A series of cyclic pentapeptides were created and tested for their effects on human melanocortin receptors, focusing on the impact of alkyl chain length in omega-amino acids.
- Compound 2 emerged as a potent agonist for the hMC-4R receptor, demonstrating significantly higher potency compared to alpha-MSH with an EC50 value of 15.4 nM.
- Additionally, Compound 2 exhibited a strong selectivity for hMC-4R over hMC-1R, highlighting the importance of lactam ring size and structure in developing selective agonists.