Home
Resources
Publications
Design, Synthesis, and Biological Evaluation of Novel Investigational Nonapeptide KISS1R Agonists With Testosterone-Suppressive Activity

Design, Synthesis, and Biological Evaluation of Novel Investigational Nonapeptide KISS1R Agonists With Testosterone-Suppressive Activity

Taiji Asami, Naoki Nishizawa, Hisanori Matsui, Kimiko Nishibori, Yoshihiro Ishibashi, Yasuko Horikoshi, Masaharu Nakayama, Shin-ichi Matsumoto, Naoki Tarui, Masashi Yamaguchi, Hirokazu Matsumoto, Tetsuya Ohtaki, etc.

J Med Chem. 2013 Nov 14;56(21):8298-307.

PMID: 24047141

Abstract:

Metastin/kisspeptin is a 54 amino acid peptide ligand of the KISS1R receptor and is a critical regulator of GnRH secretion. The N-terminally truncated peptide, metastin(45-54), possesses a 10-fold higher receptor-binding affinity than full-length metastin and agonistic KISS1R activity but is rapidly inactivated in rodent plasma. We have developed a decapeptide analog [D-Tyr(45),D-Trp(47),azaGly(51),Arg(Me)(53)]metastin(45-54) with improved serum stability compared with metastin(45-54) but with decreased KISS1R agonistic activity. Amino acid replacements at positions 45-47 led to an enhancement of KISS1R agonistic activity and metabolic stability. N-terminal truncation resulted in a stable nonapeptide, [D-Tyr(46),D-Pya(4)(47),azaGly(51),Arg(Me)(53)]metastin(46-54), compound 26, which displayed KISS1R binding affinities comparable to metastin(45-54) and had improved serum stability. Compound 26 reduced plasma testosterone in male rats and is the first short-length metastin analog to possess testosterone suppressive activities. Compound 26 has led to the elucidation of investigational analogs TAK-683 and TAK-448, both of which have undergone clinical evaluation for hormone-dependent diseases such as prostate cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4249363	Metastin (45-54)			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: