IP Library › Patent Application 12055164
Patent Application
App. No. 12/055,164

Selective Inhibitors of Nuclear Factor KappaB Activation and Uses Thereof

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Patent No.
US None
App. No.
12/055,164
Abstract

The present invention provides cell permeable NF-κB inhibitors consist of a polypeptide derived from the p65 subunit of NF-κB and a protein transduction domain derived from antennapedia third helix sequence. The inhibitor suppressed NF-κB activation induced by TNF, LPS, IL-1, okadaic acid, PMA, H 2 O 2 and cigarette smoke condensate. NF-κB-regulated reporter gene expression induced by TNF, TNFR1, TRADD, TRAF2, NIK, IKK and p65 was suppressed by the inhibitor. The inhibitor enhanced TNF- and chemotherapeutic agent-induced apoptosis. Overall these results demonstrate a NF-κB inhibitor that can selectively inhibit NF-κB activation induced by various inflammatory stimuli, down-regulate NF-κB mediated gene expression and upregulate apoptosis.

Claims (34)

1 - 14 . (canceled)

15 . A method of treating cancer in an individual, comprising the step of administering to the individual a composition comprising:

(a) a polypeptide comprising (i) a sequence selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13; and (ii) a transduction sequence selected from the group consisting of SEQ ID NO:3, a herpes virus structural protein transduction sequence, and HIV tat protein; and

(b) a pharmaceutically acceptable carrier.

16 . The method of claim 15 , further comprising the step of administering to said individual a chemotherapeutic agent.

17 . The method of claim 16 , wherein the chemotherapeutic agent is doxorubicin or cisplatin.

18 . The method of claim 15 , wherein the cancer is metastatic cancer.

19 . The method of claim 15 , wherein the composition is administered intraperitoneally, intramuscularly, subcutaneously, intravenously, or orally.

20 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:5.

21 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:6.

22 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:7.

23 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:8.

24 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:9.

25 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:11.

26 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:12.

27 . The method of claim 15 , wherein the polypeptide comprises SEQ ID NO:13.

28 . The method of claim 15 , wherein the transduction sequence is SEQ ID NO:3.

29 . The method of claim 15 , wherein the transduction sequence is a herpes virus structural protein transduction sequence.

30 . The method of claim 15 , wherein the transduction sequence is HIV tat protein.

31 . The method of claim 15 , wherein the polypeptide consists of (i) a sequence selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13; and (ii) a transduction sequence selected from the group consisting of SEQ ID NO:3, a herpes virus structural protein transduction sequence, and HIV tat protein.

32 . The method of claim 31 , wherein the transduction sequence is SEQ ID NO:3.

33 . The method of claim 31 , wherein the transduction sequence is a herpes virus structural protein transduction sequence.

34 . The method of claim 31 , wherein the transduction sequence is HIV tat protein.

35 . A method of treating cancer in an individual, comprising the step of administering to the individual a composition comprising:

(a) a polypeptide comprising SEQ ID NO:4 or SEQ ID NO:10; and

(b) a pharmaceutically acceptable carrier.

36 . The method of claim 35 , wherein the polypeptide comprises SEQ ID NO:4.

37 . The method of claim 35 , wherein the polypeptide comprises SEQ ID NO:10.

38 . The method of claim 35 , wherein the polypeptide consists of SEQ ID NO:4.

39 . The method of claim 35 , wherein the polypeptide consists of SEQ ID NO:10.

40 . The method of claim 35 , further comprising the step of administering to said individual a chemotherapeutic agent.

41 . The method of claim 40 , wherein the chemotherapeutic agent is doxorubicin or cisplatin.

42 . The method of claim 35 , wherein the cancer is metastatic cancer.

43 . The method of claim 35 , wherein the composition is administered intraperitoneally, intramuscularly, subcutaneously, intravenously, or orally.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2018
From: RESEARCH DEVELOPMENT FOUNDATION
To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 045161/0825 →