Patent ID: 8691761

Claim:
A somatostatin antagonist that binds to SSTR2; is not significantly internalized into cells expressing SSTR2, and reduces octreotide-induced internalization of SSTR2, wherein the antagonist is a cyclic somatostatin (SRIF) peptide antagonist comprising the amino acid sequence (cyclo 3-14) Xaa 1 -Xaa 2 -D-Xaa 3 -Xaa 4 -Xaa 5 -Xaa 6 -Xaa 7 -Xaa 8 -Xaa 9 -Xaa 10 -Xaa 11 -Xaa 12 -Xaa 13 -Xaa 14 -Xaa 15 ; Xaa 1 is des-Xaa; Xaa 2 is Trp(A), Phe(B), Nal or Tyr, wherein A is H, Cl, F, Br, Me, NO 2 , OMe or N-formyl and B is H, halogen, CH 3 , NO 2 or OCH 3 ; D-Xaa 3 is D-Cys, D-Pen, D-HCys or another D-isomer α-amino acid having an SH-side chain; Xaa 4 , Xaa 5 and Xaa 6 are des-Xaa; Xaa 7 is Aph(Q 1 ), Tyr, ITyr, Ala(thienyl) or Trp(A) where Q 1 is Cbm, OH—Cbm, CH 3 -Cbm, OCH 3 -Cbm, OEt-Cbm, Cbm-Et(OEt) 2 or Hor; Xaa 8 is D-Trp(A), Trp(A), Tyr, D-Tyr, Phe(B), D-Phe(B), L or D-BzlHis, L or D-(DNP)His, L or D-Aph(Cbm); Xaa 9 is Lys, N α MeLys, hLys, N α MehLys, Orn or N α MeOrn; Xaa 10 is Thr, Ser or Val; Xaa 11 , Xaa 12 and Xaa 13 are des-Xaa; Xaa 14 is Cys, Pen, hCys or another L-isomer α-amino acid having an SH side chain; Xaa 15 is 2Nal, D-2Nal, Aph(Q 2 ), D-Aph(Q 2 ), (R 1 )Cha, (R 1 )D-Cha, (R 1 )Leu, (R 1 )D-Leu, Tyr, D-Tyr, Trp, D-Trp or des-Xaa; wherein R 1 is H or C α Me, and Q 2 is Cbm, OH-Cbm, CH 3 -Cbm, OCH 3 -Cbm or OEt-Cbm; and Xaa 15 is optionally amidated or is C-terminated with Gly-OH group.