ZINC COMPLEXES AND THEIR USES

Abstract

##STR00001##

A zinc complex of a compound where the zinc complex is either a complex of JBIR-141 and a zinc ion and has the chemical formula C.sub.31H.sub.48N.sub.6O.sub.11Zn, or when the zinc complex is a complex of JBIR-142 and a zinc ion and has the chemical formula C.sub.31H.sub.48N.sub.6O.sub.12Zn.

Claims

1: A zinc complex of a compound which has the chemical structure: ##STR00009## where R═H and the compound is known as JBIR-141, or where RAH and the compound is known as JBIR-142, and the zinc complex is either a complex of JBIR-141 and a zinc ion and has the chemical formula C.sub.31H.sub.48N.sub.6O.sub.11Zn, or is a complex of JBIR-142 and a zinc ion and has the chemical formula C.sub.31H.sub.48N.sub.6O.sub.12Zn.

2: A zinc complex as defined in claim 1 for use as a medicament.

3: A zinc complex as defined in claim 1 for use in the treatment of diseases associated with the overexpression of FoxO transcription factors.

4: A zinc complex as defined in claim 1 for use in the treatment of diseases associated with the overexpression and predominantly nuclear localisation of FoxO transcription factors.

5: A zinc complex as defined in claim 1 for use in the treatment of cancer associated with the overexpression of FoxO transcription factors.

6: A zinc complex as defined in claim 1 for use in the treatment of cancer associated with the overexpression and predominantly nuclear localisation of FoxO transcription factors.

7: A zinc complex as defined in claim 1 for use in the treatment of acute or chronic myeloid leukaemia.

8: A pharmaceutical composition comprising a zinc complex according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, and one or more pharmaceutically acceptable excipients or carriers.

Description

FIGURE LEGENDS

[0076] FIG. 1: HPLC trace (λ=254 nm) of a purified sample of S149. The four peaks obtained, —(Peaks 0-3) are labelled above by numbers.

[0077] FIG. 2: Mass spectrometry data obtained when material from Peak 1 (Panel A); Peak 2 (Panel B) and Peak 3 (Panel C) was analysed. The masses of the major ions are shown above the relevant peaks.

[0078] FIG. 3: MS-MS mass spectrometry data obtained when the ˜m/z=745.27 [M+H.sup.+] ion from Peak 1 (Panel A); Peak 2 (Panel B) and Peak 3 (Panel C) was analysed. The masses of the major ions are shown above the relevant peaks.

[0079] FIG. 4: Mass spectrometry data obtained when material from Peak 0 was analysed (Panel A); MS-MS data obtained when the ˜m/z=745.2755 [M+H.sup.+] ion from Peak 0 (Panel B) was analysed; MS-MS data obtained when the ˜m/z=683.3614 [M+H.sup.+] ion from Peak 0 (Panel C) was analysed. The masses of the major ions are shown above the relevant peaks.

[0080] FIG. 5: Mass spectrometry data illustrating the isotope profile of the m/z=745.2735 [M+H.sup.+] ion (Panel A) and modelling data for the ion with the predicted formula C.sub.31H.sub.48N.sub.6O.sub.11ZnH.sup.+(Panel B).

[0081] FIG. 6: HPLC Absorbance spectra data obtained when material from Peak 0 (Panel A); Peak 1 (Panel B) and Peak 2 (Panel C) was analysed.

[0082] FIG. 7: Diagram illustrating the structure of JBIR-141. This is also the structure of the zinc-free form of S149 (as determined by Medina™ Ltd) and is the bioactive entity from Peak 0.

[0083] FIG. 8: Dose response data obtained after 72 hr treatment of MSC with S149.

[0084] FIG. 9: Dose response data obtained after 72 hr treatment of Kasumi-1 with S149.

[0085] FIG. 10: Dose response data obtained after 72 hr treatment of SKNO-1 with S149.

[0086] FIG. 11: Dose response data obtained after 72 hr treatment of HL-60 with S149.

[0087] FIG. 12: Dose response data obtained after 72 hr treatment of OCI-AML3 with S149.

[0088] FIG. 13: Dose response data obtained after 72 hr treatment of THP-1 with S149.

[0089] FIG. 14: Dose response data obtained after 72 hr treatment of MV-4-11 with S149.

[0090] FIG. 15: Dose response data obtained after 72 hr treatment of Ramos with S149.

[0091] FIG. 16: Dose response data obtained after 72 hr treatment of BL-41 with S149.

[0092] FIG. 17: Table providing S149 ECK, data for leukaemia cell lines and MSC control.