Medicinal chemistry of somatostatin analogs leading to the DTPA and DOTA conjugates of the multi-receptor-ligand SOM230.
The somatostatin field has been a success story in terms of medicinal chemistry and drug discovery offering a variety of therapeutic opportunities. A rational medicinal chemistry approach capitalising on structure activity relationships has led to the discovery of SOM230, a novel, stable cyclohexapeptide somatostatin analog which exhibits multi-receptor binding to human somatostatin receptor (SSTR) subtypes (SSTR 1-5). Recently, we extended this research utilising the hydroxproline urethane extension of SOM230 for the attachment of the chelators DTPA and DOTA, which enable early diagnosis of SSTR positive tumors and radiotherapy.
Lewis
I
I
Novartis Institutes of Biomedical Research, Basel, Switzerland. Ian.lewis@novartis.com
Albert
R
R
Kneuer
R
R
Pless
J
J
Simeon
C
C
Kerrad
S
S
Hoyer
D
D
Bruns
C
C
D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry; D007553:Isotope Labeling; D009369:Neoplasms / Q000737:chemistry / Q000532:radiotherapy; D004369:Pentetic Acid / Q000737:chemistry*; D017481:Receptors, Somatostatin / Q000032:analysis / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D013678:Technology, Pharmaceutical; D014520:Urethane / Q000737:chemistry
D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D017481:Receptors, Somatostatin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D014520:Urethane; D013004:Somatostatin; D004369:Pentetic Acid; C517782:pasireotide; D006909:Hydroxyproline