Camptothecin-peptide conjugates and pharmaceutical compositions containing the same

A conjugate comprising at least one camptothecin, wherein said conjugate has the following formula (VI):

• wherein X represents a cell penetrating peptide (CPP), which is attached to the remainder of the conjugate by a thioether bond, wherein the cell penetrating peptide comprises an amino acid sequence selected from the group consisting of:
• DPV3 (SEQ ID NO:
• 1):
• Arg Lys Lys Arg Arg Arg Glu Ser Arg Lys Lys Arg Arg Arg Glu Ser
• DPV6 (SEQ ID NO:
• 2):
• Gly Arg Pro Arg Glu Ser Gly Lys Lys Arg Lys Arg Lys Arg Leu Lys Pro
• DPV7 (SEQ ID NO:
• 3):
• Gly Lys Arg Lys Lys Lys Gly Lys Leu Gly Lys Lys Arg Asp Pro
• DPV7b (SEQ ID NO:
• 4):
• Gly Lys Arg Lys Lys Lys Gly Lys Leu GIy Lys Lys Arg Pro Arg Ser Arg
• DPV10 (SEQ ID NO:
• 5):
• Ser Arg Arg Ala Arg Arg Ser Pro Arg His Leu Gly Ser Gly
• DPV3/10 (SEQ ID NO:
• 6):
• Arg Lys Lys Arg Arg Arg Glu Ser Arg Arg Ala Arg Arg Ser Pro Arg His Leu
• DPV10/6 (SEQ ID NO:
• 7):
• Ser Arg Arg Ala Arg Arg Ser Pro Arg Glu Ser Gly Lys Lys Arg Lys Arg Lys Arg
• DPV1047 (SEQ ID NO:
• 8):
• Val Lys Arg Gly Leu Lys Leu Arg His Val Arg Pro Arg Val Thr Arg Met Asp Val
• DPV1048 (SEQ ID NO:
• 9):
• Val Lys Arg Gly Leu Lys Leu Arg His Val Arg Pro Arg Val Thr Arg Asp Val
• DPV15 (SEQ ID NO:
• 10):
• Leu Arg Arg Glu Arg Gln Ser Arg Leu Arg Arg Glu Arg Gln Ser Arg and
• DPV15b (SEQ ID NO:
• 11):
• Gly Ala Tyr Asp Leu Arg Arg Arg Glu Arg Gln Ser Arg Leu Arg Arg Arg Glu Arg Gln Ser Arg;
• Y represents the camptothecin and is represented by:
• wherein t is 0, 1 or 2 and Z is a —COO—group or a substituted or unsubstituted divalent alkyl group;
• Y is attached to the remainder of the conjugate by an ester bond, a carbonyl-disulfide bond or a carboxy-thioester bond;
• B is a cyclo(C3—C8)alkyl,
• R1 is a (C1—C8) alkyl, optionally interrupted by at least one cycloalkyl group, and optionally interrupted by at least one divalent radical selected from —CONR′—and —NR″OC(O) —, wherein R′ and R″ independently from each other are selected from hydrogen and (C1—C8) alkyl;
• and R2 is a (C1—C8) alkyl interrupted by at least one cycloalkyl group, said (C1—C8) alkyl optionally interrupted by at least one divalent radical selected from —OC(O)—, —CO2—, —CONR′—, —NR′CO—, —OC(O)NR′—, and —NR″C(O)2—, wherein R′ and R″ independently from each other are selected from hydrogen and (C1—C8) alkyl.