Granted Patent B2

US 10,849,873 · App. 16/242,950 · Granted Dec 1, 2020

Inventors: Mitchell S. Steiner (Germantown, TN); Ramesh Narayanan (Cordova, TN); Sunjoo Ahn (Daejeon, KR); James T. Dalton (Ann Arbor, MI)

Assignee: ONCTERNAL THERAPEUTICS, INC

A61K31/277A61K31/167A61K31/404A61K31/4704A61P35/00A61K9/0014A61K9/0019A61K9/0024A61K9/0053A61K9/02A61K9/06A61K9/08A61K9/10A61K9/107A61K9/1605A61K9/4866

Abstract

Claims (21)

1. A method of treating AR-positive and ER-positive breast cancer in a subject, comprising a step of determining the 18 F-16β-fluoro-5α-dihydrotestosterone ( 18 F-DHT) tumor uptake and identifying said subject as having AR-positive and ER-positive breast cancer based on 18 F-DHT tumor uptake, followed by administering to said AR-positive and ER-positive breast cancer subject a selective androgen receptor modulator (SARM) compound, wherein said selective androgen receptor modulator (SARM) compound is represented by a structure of formula I:

wherein

X is O;

G is O;

T is OH or OR;

R is alkyl;

R 1 is CH 3 ;

R 2 is H;

R 3 is H;

Z is CN;

Y is CF 3 , F, Br, Cl, I, or CN;

Q is CN, alkyl, or N(R) 2 ;

n is 1; and

m is 1.

2. The method of claim 1 wherein said AR-positive breast cancer is ER-positive.

3. The method of claim 1 wherein said AR-positive and ER-positive breast cancer is metastatic.

4. The method of claim 1 , wherein said AR-positive and ER-positive breast cancer is any one of AR-positive and ER-positive refractory breast cancer; AR-positive and ER-positive metastatic breast cancer; AR-positive and ER-positive advanced breast cancer; or AR-positive and ER-positive 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.

5. The method of claim 1 , comprising administering an optical isomer, a racemic mixture containing a SARM compound, 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.

6. 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.

7. The method of claim 6 , 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.

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

Assignments (3)

Continuity (10)