Method of treating ER mutant expressing breast cancers with selective androgen receptor modulators (SARMs)

Patent metadata

Field	Value
Publication number	US-10987334-B2
Application number	US-201816051042-A
Country	US
Kind code	B2
Filing date	Jul 31, 2018
Priority date	Jul 13, 2012
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), abemaciclib (Vorzenio)), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and/or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2-positive; and/or treating a subject suffering from ER mutant expressing breast cancer, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

First claim

What is claimed is:

1. A method of treating a subject suffering from ER mutant expressing breast cancer, comprising a step of administering to said subject a selective androgen receptor modulator (SARM) compound represented by a structure of formula II:

wherein
X is O;
G is O;
T is OH;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH 2 F, CHF 2 , CF 3 , CF 2 CF 3 , aryl, phenyl, halogen, alkenyl or OH;
R 1 is CH 3 ;
Z is NO 2 or CN;
Y is CF 3 , F, Br, Cl, I, or CN;
Q is CN, alkyl, halogen, NHCOR, NHCOOR, CONHR, NHCSCH 3 , NHCSCF 3 , or NHCSR;
wherein said ER mutant expressing breast cancer is Y537S mutation expressing breast cancer, and wherein said treating does not include preventing.

2. The method of claim 1 , comprising administering an optical isomer, a racemic mixture, a metabolite, a pharmaceutically acceptable salt, a pharmaceutical product, a hydrate, an N-oxide, or a crystal of said selective androgen receptor modulator, or any combination thereof.

3. The method of claim 1 , wherein said administering comprises intravenously, intraarterially, or intramuscularly injecting to said subject said pharmaceutical product in liquid form; subcutaneously implanting in said subject a pellet containing said pharmaceutical product; orally administering to said subject said pharmaceutical product in a liquid or solid form; or topically applying to the skin surface of said subject said pharmaceutical product.

4. The method of claim 2 , wherein said pharmaceutical product is a pellet, a tablet, a capsule, a solution, a suspension, an emulsion, an elixir, a gel, a cream, a suppository or a parenteral formulation.

5. The method of claim 1 , wherein said SARM compound is represented by a structure of Formula:

Assignees

• Gtx Inc
• Univ Tennessee Res Found

Inventors

• Narayanan Ramesh
• Ponnusamy Thamarai

Classifications

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/4866

  Organic macromolecular compounds · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/02

  Suppositories; Bougies; Bases therefor; {Ovules}(apparatus for making A61J3/08; devices for introducing into the body A61M31/00) · CPC title