PEPTIDE-CYTOTOXIC CONJUGATES COMPRISING CAMPTHOECIN AND A SOMATOSTATIN

摘要

Disclosed is a compound according to Formula (IA): A-B-C-E (IA) wherein: A is camptothecin or a derivative thereof; B is rvAhp, rvAla, rvAnc, rvApn, rvArg, rvAsp, ryCha, rvDap(Z), rvGlu or rvPhe; C is D'- D2-D3-D4 wherein D1 is glutaryl, succinyl, or deleted, D2 is (Doc)m wherein m is, independently for each occurrence thereof, 4, 5 or 6 or [Peg]x, wherein x is, independently for each occurrence thereof, 0-100; D3 is (Aepa)n wherein n is, independently for each occurrence thereof, 0 or 1; and D4 is D-Phe or Lys-D-Tyr-D-Tyr; E is a somatostatin analog of the formula c(Cys-A2-A3-D-Trp-Lys-A6-Cys)-A8-R wherein A2 is Phe or deleted; A3 is Phe, 3-(I)Tyr or Tyr, A6 is Abu, Thr or deleted; A8 is Thr or deleted; and R is NH2 or OH; or a pharmaceutically acceptable salt thereof. Also disclosed is a use of the compound, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for treating a disease or condition in a subject in need thereof, wherein said disease or condition is characterized by undesired proliferation of cells that express one or more somatostatin receptors.