Compositions and methods for treating cancer

Patent metadata

Field	Value
Publication number	US-2019117663-A1
Application number	US-201716091492-A
Country	US
Kind code	A1
Filing date	Apr 4, 2017
Priority date	Apr 4, 2016
Publication date	Apr 25, 2019
Grant date	—

Abstract

A method of treating cancer in a subject in need thereof includes administering to the subject therapeutically effective amounts of a PP2A activator and a BER inhibitor, such a PARP inhibitor.

First claim

What is claimed is:

1 . A method for treating cancer in a subject in need thereof comprising:
administering to the subject therapeutically effective amounts of a PP2A activator and BER inhibitor.

2 . The method of claim 1 , wherein the subject is administered a pharmaceutical composition including a coformulation of the PP2A activator and the BER inhibitor.

3 . The method of claim 1 , wherein the cancer is characterized by cancer cells in which PP2A has reduced activity.

4 . The method of claim 1 , wherein the cancer is characterized by cancer cells in which Plk1 is overexpressed.

5 . The method of claim 1 , wherein said cancer is high grade serious ovarian cancer.

6 . The method of claim 1 , wherein the subject has BRCA genotype not associated with an increased risk of hereditary breast-ovarian cancer syndrome

7 . The method of claim 1 , wherein the subject has a BRCA genotype associated with an increased risk of hereditary breast-ovarian cancer syndrome.

8 . The method of claim 1 , wherein the PP2A activator is a small molecule.

9 . The method of claim 8 , wherein the PP2A activator is a trycyclic neuroleptic compound or derivative thereof.

10 . The method of claim 1 , wherein the PP2A activator is a tricyclic neuroleptic compound devoid of GPCR or monoamine transporter pharmacology.

11 . The method of claim 1 , wherein the BER inhibitor is a PARP inhibitor.

12 . The method of claim 11 , wherein the PARP inhibitor is a PARP1 inhibitor selected from group consisting of nicotinamide; NU1025; 3-aminobenzamide; 4-amino-1,8-naphthalimide; 1,5-isoquinolinediol; 6(5H)-phenanthriddinone; 1,3,4,5,-tetrahydrobenzo(c)(1,6)- and (c)(1,7)-naphthyridin-6 ones; adenosine substituted 2,3-dihydro-1H-isoindol-1-ones; AG14361; AG014699; 2-(4-chlorophenyl)-5-quinoxalinecarboxamide; 5-chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazo-linone; isoindolinone derivative INO-1001; 4-hydroxyquinazoline; 2-[3-[4-(4-chlorophenyl) 1-piperazinyl]propyl]-4-3(4)-quinazolinone; 1,5-dihydroxyisoquinoline (DHIQ); 3,4-dihydro-5[4-(1-piperidinyl)(butoxy)-1(2H)-isoquinolone; CEP-6800; GB-15427; PJ34; DPQ; BS-201; AZD2281 (Olaparib); BS401; CHP101; CHP102; INH2BP; BSI201; BSI401; TIQ-A; an imidazobenzodiazepine; 8-hydroxy-2-methylquinazolinone (NU1025), CEP 9722, MK 4827, LT-673; 3-aminobenzamide; Olaparib (AZD2281; ABT-888 (Veliparib); BSI-201 (Iniparib); Rucaparib (AG-014699); INO-1001; A-966492; PJ-34 is an EGFR inhibitor selected from erlotinib, gefitinib, lapatinib, and icotinib.

13 . A method for treating cancer in a subject in need thereof comprising:
administering to the subject therapeutically effective amounts of a PP2A activator and a PARP inhibitor.

14 . The method of claim 13 , wherein the subject is administered a pharmaceutical composition including a coformulation of the PP2A activator and the BER inhibitor.

15 . The method of claim 13 , wherein the cancer is characterized by cancer cells in which PP2A has reduced activity.

16 . The method of claim 13 , wherein the cancer is characterized by cancer cells in which Plk1 is overexpressed.

17 . The method of claim 13 , wherein said cancer is high grade serious ovarian cancer.

18 . The method of claim 13 , wherein the subject has BRCA genotype not associated with an increased risk of hereditary breast-ovarian cancer syndrome

19 . The method of claim 13 , wherein the subject has a BRCA genotype associated with an increased risk of hereditary breast-ovarian cancer syndrome.

20 . The method of claim 13 , wherein the PP2A activator is a small molecule.

21 . The method of claim 13 , wherein the PP2A activator is a trycyclic neuroleptic compound or derivative thereof.

22 . The method of claim 13 , wherein the PP2A activator is a tricyclic neuroleptic compound devoid of GPCR or monoamine transporter pharmacology.

23 . The method of claim 13 , wherein the PARP inhibitor is a PARP1 inhibitor selected from group consisting of nicotinamide; NU1025; 3-aminobenzamide; 4-amino-1,8-naphthalimide; 1,5-isoquinolinediol; 6(5H)-phenanthriddinone; 1,3,4,5,-tetrahydrobenzo(c)(1,6)- and (c)(1,7)-naphthyridin-6 ones; adenosine substituted 2,3-dihydro-1H-isoindol-1-ones; AG14361; AG014699; 2-(4-chlorophenyl)-5-quinoxalinecarboxamide; 5-chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazo-linone; isoindolinone derivative INO-1001; 4-hydroxyquinazoline; 2-[3-[4-(4-chlorophenyl) 1-piperazinyl]propyl]-4-3(4)-quinazolinone; 1,5-dihydroxyisoquinoline (DHIQ); 3,4-dihydro-5[4-(1-piperidinyl)(butoxy)-1(2H)-isoquinolone; CEP-6800; GB-15427; PJ34; DPQ; BS-201; AZD2281 (Olaparib); BS401; CHP101; CHP102; INH2BP; BSI201; BSI401; TIQ-A; an imidazobenzodiazepine; 8-hydroxy-2-methylquinazolinone (NU1025), CEP 9722, MK 4827, LT-673; 3-aminobenzamide; Olaparib (AZD2281; ABT-888 (Veliparib); BSI-201 (Iniparib); Rucaparib (AG-014699); INO-1001; A-966492; PJ-34 is an EGFR inhibitor selected from erlotinib, gefitinib, lapatinib, and icotinib.

Assignees

• Univ Case Western Reserve

Inventors

• Difeo Analisa
• Narla Goutham
• Armstrong Amy D

Classifications

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/538 Primary

  ortho- or peri-condensed with carbocyclic ring systems · CPC title

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title