Medical Use

Abstract

The invention provides a molecule that inhibits or prevents an interaction between a Src family kinase and an androgen or estradiol receptor, for use in preventing or treating a non-cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject, or for use in preventing or treating a cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject who wishes to preserve fertility, or for use in preventing or treating a gynaecological condition in which an activity of AR and/or ER is a contributory factor in a subject. Preferably, the molecule comprises or consists of the structure: B j -[(Pro) n -X r His-Pro-His-Ala-Arg-Ile-Lys] m -R p , or B j -[lys-ile-arg-ala-his-pro-his-x r -(pro) n ] m -R p , or a derivative or fragment thereof, wherein B is a first chemical moiety, j is 0 or 1, n is an integer from 1-10, X is any amino acid, r is an integer from 0 to 2, m is an integer from 1 to 3, R is a second chemical moiety, p is 0 or 1, and [lys-ile-arg-ala-his-pro-his-x r -(pro) n ] is the retro-inverso peptide of [(Pro) n -X r -His-Pro-His-Ala-Arg-Ile-Lys].

1 . A molecule that inhibits or prevents an interaction between a Src family kinase and an androgen receptor (AR) or estradiol receptor (ER), for use in preventing or treating a non-cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject, or for use in preventing or treating a cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject who wishes to preserve fertility, or for use in preventing or treating a gynaecological condition in which an activity of AR and/or ER is a contributory factor in a subject. 
     
     
         2 . (canceled) 
     
     
         3 . A method of preventing or treating a non-cancerous condition in which an activity ofan androgen receptor (AR) and/or estradiol receptor (ER) is a contributory factor in a subject, or for preventing or treating a cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject who wishes to preserve fertility, or for preventing or treating a gynaecological condition in which an activity of AR and/or ER is a contributory factor in a subject, the method comprising administering to the subject in need thereof an effective amount of a molecule that inhibits or prevents an interaction between a Src family kinase and an AR or ER. 
     
     
         4 . The molecule of  claim 1 , wherein the Src family kinase is any of Src, Yes, Fyn, Fgr, Lck, Hck, Blk, Lyn and Frk. 
     
     
         5 . The molecule of  claim 1 , wherein the molecule comprises the structure:
 B j -[(Pro) n -X r -His-Pro-His-Ala-Arg-Ile-Lys] m -R p  (SEQ ID NO: 1), or B j -[lys-ile-arg-ala-his-pro-his-x r -(pro) n ] m -R p  (SEQ ID NO: 2), or a derivative or fragment thereof,
 wherein B is a first chemical moiety, j is 0 or 1, n is an integer from 1-10, X is any amino acid, r is an integer from 0 to 2, m is an integer from 1 to 3, R is a second chemical moiety, p is 0 or 1, and [lys-ile-arg-ala-his-pro-his-x r -(pro) n ] (SEQ ID NO: 2) is the retro-inverso peptide of [(Pro) n -X r -His-Pro-His-Ala-Arg-Ile-Lys] (SEQ ID NO: 1). 
   
     
     
         6 . The molecule of  claim 1 , wherein the molecule is an antibody against the SH3 or SH2 domain of a Src family kinase or wherein the molecule is an antibody against the peptide (Pro) n -X r -His-Pro-His-Ala-Arg-Ile-Lys (SEQ ID NO: 1 ), where n is an integer from 1-10, X is any amino acid and r is an integer from 0 to 2. 
     
     
         7 . (canceled) 
     
     
         8 . The molecule of  claim 5 , wherein n is 3 and m is 1. 
     
     
         9 . The molecule of  claim 1 , wherein the molecule is a peptide, preferably wherein the peptide is between 3 and 57 amino acids in length. 
     
     
         10 . (canceled) 
     
     
         11 . The molecule, use or method of  claim 5 , wherein B is any of H, an acetyl group, or one or more amino acids provided with a free or acetyl-derivatised NH 2  group. 
     
     
         12 . The molecule of  claim 5 , wherein R is any of an OH group, an NH 2  group, or one or more amino acids with a C-terminal carboxy-amide group. 
     
     
         13 . The molecule of  claim 5 , wherein the first and second chemical moieties B and R comprise independently or both comprise any of a lipid, a fatty acid, a polyethylene glycol, a triglyceride, glycerol, a prenyl or isoprenyl moiety, a carbohydrate, an amino acid, a peptide, a polypeptide, or a nucleic acid, or a combination thereof. 
     
     
         14 . The molecule of  claim 5 , wherein r is 0. 
     
     
         15 . The molecule of  claim 5 , wherein the molecule comprises the structure Pro-Pro-Pro-His-Pro-His-Ala-Arg-Ile-Lys (SEQ ID NO: 21) or Ac-Pro-Pro-Pro-His-Pro-His-Ala-Arg-Ile-Lys-NH 2  (SEQ ID NO: 21), where Ac is an acetyl group. 
     
     
         16 . The molecule of  claim 5 , wherein X is threonine and r is 1. 
     
     
         17 . The molecule of  claim 16 , wherein the molecule comprises the structure Pro-Pro-Thr-His-Pro-His-Ala-Arg-Ile-Lys (SEQ ID NO: 23), or Ac-Pro-Pro-Thr-His-Pro-His-Ala-Arg-Ile-Lys-NH 2  (SEQ ID NO: 23), where Ac is an acetyl group. 
     
     
         18 . The molecule of  claim 5 , wherein the molecule comprises a structure selected from the group consisting of HPHARIK (SEQ ID NO: 3), HPHAR (SEQ ID NO: 4), PHPHAR (SEQ ID NO: 5), HPH, PHPH (SEQ ID NO: 6), PPHPH (SEQ ID NO: 7), PPPHPH (SEQ ID NO: 8), PHP, PPHP (SEQ ID NO: 9), PPPHP (SEQ ID NO: 10), PPPH (SEQ ID NO: 11), PPH, and PPP, such as a molecule that comprises a structure selected from the group consisting of Ac-HPHARIK-NH2 (SEQ ID NO: 12), Ac-HPHAR-NH2 (SEQ ID NO: 13), Ac-PHPHAR-NH2 (SEQ ID NO: 14), Ac-HPH-NH2, Ac-PHPH-NH2 (SEQ ID NO: 15), Ac-PPHPH-NH2 (SEQ ID NO: 16), Ac-PPPHPH-NH2 (SEQ ID NO: 17), Ac-PHP-NH2, Ac-PPHP-NH2 (SEQ ID NO: 18), Ac-PPPHP-NH2P (SEQ ID NO: 19), Ac-PPPH-NH2 (SEQ ID NO: 20), Ac-PPH-NH2 and Ac-PPP-NH2, where Ac is an acetyl group. 
     
     
         19 . The method according to  claim 3 , wherein the molecule is administered as a vaccine to generate antibodies. 
     
     
         20 . The molecule of  claim 1 , wherein the molecule is linked to a carrier molecule such as bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH). 
     
     
         21 . The molecule of  claim 1 , wherein the molecule is comprised in a lipid composition such as a lipid particle, a nanocapsule, a liposome or a lipid vesicle. 
     
     
         22 . The method according to  claim 3 , wherein the non-cancerous condition is any one of endometriosis, ovarian cysts, fibroids polyps hyperplasia, neoplasia, anovulatory bleeding, or endometrial growth in the scrotum, bladder or prostate, or is a reproductive condition, such as a gynaecological condition. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 3 , wherein the cancerous condition is any one of uterine fibroids, fibroids polyps hyperplasia, ovarian cancer, bladder cancer, cervical cancer, uterine cancer, testicular cancer or prostate cancer, or is a reproductive condition, such as a gynaecological condition. 
     
     
         25 - 38 . (canceled) 
     
     
         39 . The molecule of  claim 1  formulated in any of a vaginal or rectal suppository; an intravaginal tampon; an intravaginal ring; an intravaginal pessary; an intravaginal sponge; a medicated intrauterine device (IUD); or a sustained-release formulation. 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . A method of selecting an agent to prevent or treat a non-cancerous condition in which an activity of AR and/or ER is a contributory factor, the method comprising determining whether a test agent reduces an interaction between (a) AR or ER or a portion thereof, said portion being capable of binding to a Src family kinase and (b) a Src family kinase or a portion thereof, said portion being capable of binding to AR or ER. 
     
     
         43 - 45 . (canceled)