Treatments of prostate cancer

Patent metadata

Field	Value
Publication number	US-11478496-B2
Application number	US-202217697306-A
Country	US
Kind code	B2
Filing date	Mar 17, 2022
Priority date	Jan 24, 2020
Publication date	Oct 25, 2022
Grant date	Oct 25, 2022

Abstract

The present invention provides compounds, compositions and methods for the treatment of prostate cancers, preferably, advanced prostate cancers. The subject invention also provides compounds, compositions and methods for preventing/slowing down/reducing the progress and proliferation of prostate cancer cells. The subject invention further provides compounds, compositions and methods for inhibiting DNA repair within cancer cells to slow tumor growth, preferably, by inhibiting BER capacity, including pol β and LIG I.

First claim

We claim:

1. A method for inhibiting DNA repair in a cancer cell comprising contacting the cancer cell with a composition comprising one or more compounds selected from natamycin, calcipotriene, ceftazidime, nystatin, prasugrel, sirolimus, flecainide acetate, dihydroergotamine mesylate, risperidone, dipyridamole, doxycycline monohydrate, methylergonovine maleate, paliperidone, reserpine, and sunitinib malate; and detecting an inhibitory effect on DNA Ligase I (LIG I), flap endonuclease 1 (FEN1) and/or DNA polymerase β (pol β).

2. The method of claim 1 , the cancer cell being a prostate cancer cell.

3. The method of claim 2 , the prostate cancer cell being selected from organ-confined primary prostate cancer cells, locally invasive advanced prostate cancer cells, metastatic prostate cancer cells, and castration-resistant prostate cancer (CRPC) cells.

4. The method of claim 2 , the prostate cancer cell being a CRPC cell.

5. The method of claim 1 , the composition comprising at least natamycin.

6. The method of claim 1 , the composition comprising one or more compounds selected from natamycin, calcipotriene, ceftazidime, nystatin, and prasugrel.

7. The method of claim 1 , the composition further comprising an antiandrogen agent.

8. A method for inhibiting DNA repair comprising administering, to a subject having prostate cancer, an effective amount of a pharmaceutical composition comprising one or more compounds selected from natamycin, calcipotriene, ceftazidime, nystatin, prasugrel, sirolimus, flecainide acetate, dihydroergotamine mesylate, risperidone, dipyridamole, doxycycline monohydrate, methylergonovine maleate, paliperidone, reserpine, and sunitinib malate; and detecting an inhibitory effect on LIG I, FEN1 and/or pol β.

9. The method of claim 8 , the prostate cancer being organ-confined primary prostate cancer, locally invasive advanced prostate cancer, metastatic prostate cancer, or castration-resistant prostate cancer (CRPC).

10. The method of claim 8 , the prostate cancer being CRPC.

11. The method of claim 8 , the composition comprising at least natamycin.

12. The method of claim 8 , the composition comprising one or more compounds selected from natamycin, calcipotriene, ceftazidime, nystatin, and prasugrel.

13. The method of claim 8 , the composition further comprising an antiandrogen agent.

14. The method of claim 8 , the administration being local, oral, transdermal, parenteral, intracranial, intracerebral, intraspinal, intrauterine, or rectal administration.

15. The method of claim 1 , the composition comprising one or more compounds selected from prasugrel, sirolimus, flecainide acetate, dihydroergotamine mesylate, risperidone, dipyridamole, doxycycline monohydrate, methylergonovine maleate, paliperidone, reserpine, and sunitinib malate.

16. The method of claim 8 , the pharmaceutical composition comprising one or more compounds selected from prasugrel, sirolimus, flecainide acetate, dihydroergotamine mesylate, risperidone, dipyridamole, doxycycline monohydrate, methylergonovine maleate, paliperidone, reserpine, and sunitinib malate.

Assignees

• Tse Dinh Yuk Ching
• Liu Yuan
• Agoulnik Irina
• The Florida International Univ Board Of Trustees

Inventors

• Tse-Dinh Yuk-Ching
• Liu Yuan
• Agoulnik Irina

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/7048 Primary

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61K31/4365

  the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine · CPC title

• A61K31/593

  9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3 · CPC title

• A61K31/546

  containing further heterocyclic rings, e.g. cephalothin · CPC title