US2017209521A1PendingUtilityA1

Small molecule cancer treatments that cause necrosis in cancer cells but do not affect normal cells

63
Assignee: UNIV NEW YORK STATE RES FOUNDPriority: Nov 26, 2007Filed: Dec 7, 2016Published: Jul 27, 2017
Est. expiryNov 26, 2027(~1.3 yrs left)· nominal 20-yr term from priority
Inventors:Matthew R. PincusJosef MichlEhsan Sarafraz-Yazdi
A61K 47/54A61P 35/00A61K 38/10A61K 38/03A61K 45/06A61K 31/4995C07K 14/4746A61K 38/1709A61K 31/155C07K 2319/03A61K 38/1758
63
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

A method of treating cancer in a subject, including: providing a subject having a plurality of cancer cells; and administering to the subject, a therapeutically effective amount of a composition including: an HDM-2 binding component; and a membrane resident component, the membrane resident component bound to the HDM-2 binding component. Also provided are a method of selectively necrosing cancer cells, a method of causing membranolysis in cancer cells, and a cancer treatment composition.

Claims

exact text as granted — not AI-modified
1 . A method of treating cancer in a subject, said method comprising:
 providing a subject having a plurality of cancer cells; and   administering to the subject, a therapeutically effective amount of a composition including:
 an HDM-2 binding component selected from the group consisting of: 
 12-26 p53 protein, residues (PPLSQETFSDLWKLL) (SEQ ID NO:1), 
 17-26 p53 protein, residues (ETFSDLWKLL) (SEQ ID NO:2), 
 12-26 p53 protein, residues (PPLSQETFSDLWKLL) (SEQ ID NO:1) 
 12-26 p53 protein, residues (P*P*LSQETFSDLWKLL) (SEQ ID NO:1), 
 17-26 p53 protein, residues (E*T*FSDLWKLL) (SEQ ID NO:2), 
 12-26 p53 protein, residues (P*P*L*SQETFSDLWKLL) (SEQ ID NO:1), where * denotes D-amino acid, 
   
       
         
           
           
               
               
           
         
         
           and 
           XFMXXXEXLX(SEQ ID NO. 10), where X in first position is actyl moiety (CHO), X in fourth position is alpha-amino-isobutyric acid, X in fifth position is phosphonomethyl-phenylalanine, X in sixth position is 6-chlorotryptophan, X in eighth position is 1-amino-cyclopropanecarboxylic acid, X in tenth position is NH2; and 
         
         a membrane resident component selected from the group consisting of:
 KKWKMRRNQFWVKVQRG (SEQ ID NO:3), and 
 KKWKMRRNQFWVKVQRGLLR (SEQ ID NO: 12), 
 
         said membrane resident component bound to said HDM-2 binding component. 
       
     
     
         2 . A method of treating cancer in a subject, said method comprising:
 providing a subject having a plurality of cancer cells; and   administering to the subject, a therapeutically effective amount of a composition including:
 an HDM-2 binding component selected from the group consisting of: 
 12-26 p53 protein, residues (PPLSQETFSDLWKLL) (SEQ ID NO:1), 
 17-26 p53 protein, residues (ETFSDLWKLL) (SEQ ID NO:2), 
 12-26 p53 protein, residues (PPLSQETFSDLWKLL) (SEQ ID NO:1) 
 12-26 p53 protein, residues (P*P*LSQETFSDLWKLL) (SEQ ID NO:1), 
 17-26 p53 protein, residues (E*T*FSDLWKLL) (SEQ ID NO:2), 
 12-26 p53 protein, residues (P*P*L*SQETFSDLWKLL) (SEQ ID NO:1), where * denotes D-amino acid, 
 XFMXXXEXLX, where X in first position is actyl moiety (CHO), X in fourth position is alpha-amino-isobutyric acid, X in fifth position is phosphonomethyl-phenylalanine, X in sixth position is 6-chlorotryptophan, X in eighth position is 1-amino-cyclopropanecarboxylic acid, X in tenth position is NH2 (SEQ ID NO. 10); and 
   a membrane resident component selected from the group consisting of:
 K*K*WKMRRNQFWVKVQRG (SEQ ID NO:3), 
 K*K*WKMRRNQFWVKVQRGLLR (SEQ ID NO: 12), and 
   
       
         
           
           
               
               
           
         
         said membrane resident component bound to said HDM-2 binding component. 
       
     
     
         3 . The method of  claim 1 , further comprising the step of observing in a medium of the cancer cells an early release of LDH. 
     
     
         4 . The method of  claim 1 , further comprising the step of observing membranolysis of said cancer cells. 
     
     
         5 . The method of  claim 1 , further comprising the step of observing a decrease from a number of pretreatment cancer cells to a number of post treatment cancer cells. 
     
     
         6 . The method of  claim 1 , further comprising the step of observing tumor cell eradication. 
     
     
         7 . The method of  claim 1 , further comprising the step of repeating the administering step until a result is reached. 
     
     
         8 . The method of  claim 1 , further comprising the step of observing necrosis in the cancer cells. 
     
     
         9 . The method of  claim 1 , further comprising the step of observing a non-response in the normal cell, wherein the non-response indicates the normal cell is unaffected. 
     
     
         10 . The method of  claim 1 , wherein the administering step further comprises administering a PNC-27, a PNC-28, or combinations thereof. 
     
     
         11 . The method of  claim 1 , wherein the HDM-2 binding component is 12-26 p53 protein, residues (PPLSQETFSDLWKLL) (SEQ ID NO:1). 
     
     
         12 . The method of  claim 1 , wherein the HDM-2 binding component is 17-26 p53 protein, residues (ETFSDLWKLL) (SEQ ID NO:2). 
     
     
         13 . The method of  claim 1 , wherein the membrane resident component is KKWKMRRNQFWVKVQRG (SEQ ID NO:3). 
     
     
         14 . The method of  claim 11 , wherein the membrane resident component is KKWKMRRNQFWVKVQRG (SEQ ID NO:3). 
     
     
         15 . The method of  claim 12 , wherein the membrane resident component is KKWKMRRNQFWVKVQRG (SEQ ID NO:3). 
     
     
         16 . The method of  claim 1 , further comprising the step of observing in a medium of the cancer cells an early release of LDH. 
     
     
         17 . The method of  claim 1 , further comprising the step of observing membranolysis of said cancer cells. 
     
     
         18 . The method of  claim 1 , further comprising the step of observing a decrease from a number of pretreatment cancer cells to a number of post treatment cancer cells. 
     
     
         19 . The method of  claim 1 , further comprising the step of observing tumor cell eradication. 
     
     
         20 . The method of  claim 1 , further comprising the step of repeating the administering step until a result is reached. 
     
     
         21 . The method of  claim 1 , further comprising the step of observing necrosis in the cancer cells. 
     
     
         22 . The method of  claim 2 , further comprising the step of observing a non-response in the normal cell, wherein the non-response indicates the normal cell is unaffected. 
     
     
         23 . The method of  claim 2 , wherein the administering step further comprises administering a PNC-27, a PNC-28, or combinations thereof 
     
     
         24 . The method of  claim 2 , wherein the HDM-2 binding component is 12-26 p53 protein, residues (PPLSQETFSDLWKLL) (SEQ ID NO:1). 
     
     
         25 . The method of  claim 2 , wherein the HDM-2 binding component is 17-26 p53 protein, residues (ETFSDLWKLL) (SEQ ID NO:2). 
     
     
         26 . The method of  claim 2 , wherein the membrane resident component is KKWKMRRNQFWVKVQRG (SEQ ID NO:3). 
     
     
         27 . The method of  claim 24 , wherein the membrane resident component is KKWKMRRNQFWVKVQRG (SEQ ID NO:3). 
     
     
         28 . The method of  claim 25 , wherein the membrane resident component is KKWKMRRNQFWVKVQRG (SEQ ID NO:3).

Join the waitlist — get patent alerts

Track US2017209521A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.