IP Library › Granted Patent US 12,239,656
Granted Patent B2
US 12,239,656 · App. 18/058,212 · Granted Mar 4, 2025

Nucleoporins as drug targets for anti-proliferative therapeutics

Inventor: Maximiliano D'Angelo (San Diego, CA)
Assignee: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
A61K31/7105A61K35/00C12N15/113G01N33/5011A61K45/06C12N2310/122C12N2310/141
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Quick Facts
Patent No.
US 12,239,656
App. No.
18/058,212
Granted
Mar 4, 2025
Kind
B2
Abstract

Disclosed herein are methods of inhibiting nuclear pore complex assembly and inducing nuclear pore complex disassembly. Methods to screen for agents that inhibit nuclear pore assembly or induce nuclear pore complex disassembly are also disclosed.

Claims (16)

1. A method of treating a proliferative disease or disorder in an individual in need thereof, the method comprising:

administering to the individual a therapeutically effective amount of an agent that inhibits nuclear pore complex assembly or induces nuclear pore complex disassembly, wherein the nuclear pore complex assembly is not inhibited in non-dividing cells or the nuclear pore complex disassembly is not induced in the non-dividing cells, wherein the proliferative disease or disorder is cancer, wherein the cancer has a mutation in a Ras gene, wherein the agent is a small interfering RNA (siRNA) or short hairpin RNA (shRNA), and wherein the agent targets one or more of Nup93 or Nup96 of a nuclear pore complex.

2. The method of claim 1 , wherein the agent inhibits expression of Nup93 or Nup96 of the nuclear pore complex.

3. The method of claim 1 , wherein the agent promotes degradation of Nup93 or Nup96 of the nuclear pore complex.

4. The method of claim 1 , wherein the mutation is a G12D mutation.

5. The method of claim 1 , wherein the cancer is melanoma.

6. A method of treating a proliferative disease or disorder in an individual in need thereof, the method comprising:

administering to the individual a therapeutically effective amount of an agent that inhibits nuclear pore complex assembly or induces nuclear pore complex disassembly, wherein the nuclear pore complex assembly is not inhibited in non-dividing cells or the nuclear pore complex disassembly is not induced in the non-dividing cells, wherein the proliferative disease or disorder is cancer, wherein the cancer has a mutation in a Ras gene, wherein the agent is a small interfering RNA (siRNA) or short hairpin RNA (shRNA), and wherein the agent targets one or more of Nup93 or Nup96 of a nuclear pore complex, and wherein the cancer is colorectal cancer.

7. The method of claim 1 , wherein the agent inhibits Nup96 of the nuclear pore complex.

8. The method of claim 1 , wherein the agent is small interfering RNA (siRNA).

9. The method of claim 1 , wherein the agent is short hairpin RNA (shRNA).

10. A method of treating a proliferative disease or disorder in an individual in need thereof, comprising:

administering to the individual a therapeutically effective amount of an agent that inhibits nuclear pore complex assembly or induces nuclear pore complex disassembly, wherein the nuclear pore complex assembly is not inhibited in non-dividing cells or the nuclear pore complex disassembly is not induced in the non-dividing cells, wherein the proliferative disease or disorder is cancer, wherein the cancer has a mutation in a Ras gene, and wherein the agent targets one or more of Nup93 or Nup96 of a nuclear pore complex, and wherein the agent is a small molecule or an antisense oligonucleotide.

11. The method of claim 1 , further comprising administering an additional therapeutic agent.

12. The method of claim 1 , wherein the administering to the individual the therapeutically effective amount of the agent comprises contacting a cell having a number of nuclear pore complexes with the agent, wherein the agent reduces the number of nuclear pore complexes in the cell.

13. The method of claim 1 , wherein the agent inhibits Nup93 of the nuclear pore complex.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 5, 2023
From: D'ANGELO, MAXIMILIANO
To: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
Reel/Frame 063228/0876 →
Continuity (3)
Continuation 16629463
Provisional Application 62531257 · Jul 11, 2017
Related Publication 20230172964A1 · Jun 8, 2023
References Cited (18)
US 11564937B2 · D'Angelo · 2023 [cited by applicant]
US 20100273859A1 · Elledge et al. · 2010 [cited by applicant]
US 20150023973A1 · Kwon et al. · 2015 [cited by applicant]
WO WO2018129080A1 · 2018 [cited by applicant]
WO WO2019014234A1 · 2019 [cited by applicant]
Chen et al, PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy. Oncotarget. 6(1):355-367 (2015). [cited by applicant]
David-Watine. Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells. PLoS One 6(7):e22423 (2011). [cited by applicant]
Elbashir et al. Functional anatomy of siRNAs for mediating efficient RNAi in [cited by applicant]
Higby et al., 5-Flurouracil disrupts nuclear export and nuclear pore permeability in a calcium dependent manner. Apoptosis. 22(3):393-405 (2017). [cited by applicant]
Karacosta et al., Nucleoporin 62 and Ca(2+)/calmodulin dependent kinase kinase 2 regulate androgen receptor activity in castrate resistant prostate cancer cells. Prostate 76:294-306 (2016). [cited by applicant]
MacDiarmid et al. Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug. Nat Biotechnol. 27(7):643-51 (2009). [cited by applicant]
PCTUS2018041461 International Search Report and Written Opinion dated Nov. 1, 2018. [cited by applicant]
PCT/US2018/041461 Invitation to Pay Additional Fees dated Sep. 7, 2018. [cited by applicant]
Prior et al. A comprehensive survey of ras mutations in cancer. Cancer Res 72:2457-2467 (2012). [cited by applicant]
Simon et al. Cancer and the Nuclear Pore Complex. In: Schirmer E., de las Heras J. (eds) Cancer Biology and the Nuclear Envelope. Advances in Experimental Medicine and Biology, vol. 773. Springer, New York, NY. (2014). [cited by applicant]
U.S. Appl. No. 16/629,463 Office Action dated Apr. 19, 2022. [cited by applicant]
U.S. Appl. No. 16/629,463 Office Action dated Sep. 7, 2021. [cited by applicant]
Sakuma, Stephen et al. Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death. Cancer Discov 11(1):176-193 (2021). [cited by applicant]