Chelating platform for delivery of radionuclides

Patent metadata

Field	Value
Publication number	US-2022160904-A1
Application number	US-202117643734-A
Country	US
Kind code	A1
Filing date	Dec 10, 2021
Priority date	Aug 29, 2016
Publication date	May 26, 2022
Grant date	—

Abstract

Siderocalin-metal chelator combinations that bind metallic radioisotopes used in nuclear medicine with high affinity are described. The high affinity siderocalin-metal chelator combinations include a number of chelator backbone arrangements with functional groups that coordinate with metals. The siderocalin-metal chelator combinations can be used to deliver radionuclides for imaging and therapeutic purposes.

First claim

What is claimed is:

1 . A composition comprising a compound or a salt thereof bound to a metal and a siderocalin, the compound having the structure of Formula I:

wherein:
(i) each of A1, A2, A3, and A4, individually, is a CAM group, a 1,2-HOPO group, or a HA group;
(ii) each of B1, B2, B3, and B4, individually, is an amide group or an amine group;
(iii) at least one of C1, C2, C3, C4, C5, and C6, individually, is SH;
(iv) at least another one of C1, C2, C3, C4, C5, and C6 is optional and, individually, is C(═O)OH or NH 2 ;
(v) at least one of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13, individually, is H, amine group, amide group, an alkyl group having no greater than 10 carbon atoms, an alkylamino group having no greater than 10 carbon atoms and no greater than 2 nitrogen atoms; an alkyl ether group having no greater than 10 carbon atoms, a hydroxy ester group, or an alkyl ester group having no greater than 10 carbon atoms; and
(vi) at least one of L1, L5, L6, L7, L8, L9, L10, L11, L12, and L13 is optional.

2 . The composition of claim 1 , the compound having the structure of Formula I, wherein:
at least another one of L2, L3, and L4, individually, is an amine group or an amide group; or when L1, C1, L7, C2, L9, C3, L11, C4, L13, and C5 are absent, L5 is an unsubstituted alkyl group having no greater than 5 carbon atoms, and C6 is SH.

3 . The composition of claim 1 , the compound having the structure of Formula I, wherein each of L2, L3, L4, L6, L8, L10, and L12, individually, is an unsubstituted alkyl group having no greater than 5 carbon atoms; and optionally wherein: A1 is a CAM group or a HOPO group; A2 is a HA group; A3 is a HA group; and A4 is a CAM group, a HOPO group, or a HA group.

4 . The composition of claim 1 , the compound having the structure of Formula I, wherein:
(i) at least one of L2, L3, or L4, individually, is an alkylamino group; or (ii) each of B1, B2, and B3, individually, is an amide group; B4 is an amino group; each of L2 and L3, individually, is an amino group; and L4 is an alkyl group having no greater than 5 carbon atoms; and optionally, when C1, C2, C3, C4, C5, A1, A2, A3, L1, L6, L7, L8, L9, L10, L11, L12, and L13 are absent, A4 is a CAM group, a HOPO group, or a HA group; and L5 is an alkyl group having no greater than 5 carbon atoms.

5 . The composition of claim 1 , the compound having the structure of Formula I, wherein:
(i) each of B1, B2, and B3, individually, is an amide group; B4 is an amino group; each of L2 or L3, individually, is an amino group; and L4 is an alkyl group having no greater than 5 carbon atoms; and optionally, when C1, C2, C3, C4, C5, A1, A2, A3, L1, L6, L7, L8, L9, L10, L11, and L13 are absent, L12 is an amino group, L5 is an ether group having no greater than 10 carbon atoms, and A4 is a CAM group, a HOPO group, or a HA group; or (ii) when C1, C2, C5, C6, L1, L2, L3, L4, L5, L7, L13, B2, and B4 are absent, each of 1 and B3, individually, is an amide group; each of L6, L8, L10, and L12, individually, is an amino group; each of A1, A2, A3, and A4, individually, is a CAM group, a HOPO group, or a HA group; and each of L9 and L11, individually, is an alkyl group having no greater than 5 carbon atoms.

6 . A composition comprising a compound or a salt thereof bound to a metal and a siderocalin, the compound having the structure of Formula II:

wherein:
at least one of R 1 , R 2 , R 3 , R 4 , and R 5 , individually, is a CAM group, a HA group, or a 1,2-HOPO group;
at least another one of R 1 , R 2 , R 3 , R 4 , and R 5 , individually, is H, an alkyl group having from 1 to 10 carbon atoms;
R 6 is (i) H, (ii) an alkyl group having from 1 to 10 carbon atoms, or (iii) an alkyl group having from 1 to 10 carbon atoms and substituted by at least one of SH, NH 2 , or C(═O)OH;
m can be from 1 to 6;
n can be from 1 to 6; and
o can be from 1 to 6.

7 . The composition of claim 6 , the compound having the structure of Formula III:

wherein:
at least one of R 1 , R 2 , R 3 , R 4 , and R 5 , individually, is a CAM group, a HA group, or a 1,2-HOPO group; optionally, another one of R 1 , R 3 , R 4 , or R 5 , individually, is H or an alkyl group having from 1 to 10 carbon atoms;
R 2 is H or an alkyl group including from 1 to 5 carbon atoms;
R 7 is SH, C(═O)OH, or NH 2 ; and
p is from 1 to 4;
and optionally, wherein:
R 1 is a CAM group or a 1,2-HOPO group;
each of R 3 and R 4 , individually, is a HA group; and
R 5 is a CAM group, a 1,2-HOPO group, or a HA group.

8 . The composition of claim 7 , the compound having the structure of Formula IV, V, VI or VII:

wherein:
R 7 is SH, NH 2 , or C(═O)OH;
each of R 2 , R 8 , and R 9 , individually, is H or an alkyl group including from 1 to 5 carbon atoms; and
p is from 1 to 4.

9 . The composition of claim 7 , the compound having the structure of Formula VIII or IX:

wherein:
R 7 is SH, C(═O)OH, or NH 2 ;
each of R 2 , R 8 , R 9 , and R 10 , individually, is an H or an alkyl group including from 1 to 5 carbon atoms; and
p is from 1 to 4.

10 . The composition of claim 7 , the compound having the structure of Formula X or XI:

11 . A composition comprising a compound or a salt thereof bound to a metal and a siderocalin, the compound having the structure of Formula XII:

wherein:
at least one of R 11 , R 12 , R 13 , or R 15 , individually, is a CAM group, a HA group, or a 1,2-HOPO group;
optionally, at least another one of R 11 , R 12 , R 13 , or R 15 , individually, is H, OH, or an alkyl group having from 1 to 10 carbon atoms;
R 17 is SH, C(═O)OH, or NH 2 ;
each of R 2 , R 14 , and R 16 , individually, is H, OH, or an alkyl group having from 1 to 10 carbon atoms; and
r can be from 0 to 6;
and optionally, wherein
R 11 is a CAM group or a 1,2-HOPO group;
R 12 and R 15 , individually, is a HA group; and
R 13 is a CAM group, a 1,2-HOPO group, or a HA group.

12 . The composition of claim 11 , the compound having the structure of Formula XIII, XIV, XVII, or XVIII:

wherein:
each of R 2 , R 14 , R 16 , R 18 , and R 19 , individually, is H, OH, or an alkyl group having from 1 to 10 carbon atoms;
R 17 is SH, C(═O)OH, or NH 2 ; and
r can be from 0 to 4.

13 . The composition of claim 11 , the compound having the structure of Formula XV or XVI:

wherein:
each of R 2 , R 14 , R 16 , R 13 , R

Assignees

• Hutchinson Fred Cancer Res
• Univ California

Inventors

• Strong Roland K
• Rupert Peter
• Abergel Rebecca J
• Captain Ilya
• Deblonde Gauthier Jp

Classifications

• C07K14/47

  from mammals · CPC title

• A61K51/0482 Primary

  chelates from cyclic ligands, e.g. DOTA · CPC title

• B01D15/34

  Size-selective separation, e.g. size-exclusion chromatography; Gel filtration; Permeation · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C22B60/02

  Obtaining thorium, uranium, or other actinides · CPC title