HEXIMI as a suppressor of HIV replication and cardiac hypertrophy

Abstract

Cellular transcription is modulated by increasing or decreasing the amount of active HEXIM1 in the cell. The methods are applied to the treatment of HIV infection and cardiac hypertrophy. Assays using reconstituted 7SK:P-TEFb snRNP screen for agents that modulate HEXIM1-P-TEFb binding.

1 - 18 . (canceled)  
   
   
       19 . A method for inhibiting HIV replication in a patient, the method comprising the steps of: 
 determining that the patient is HIV-infected and a target for HEXIM1 therapy;    increasing the amount of active HEXIM1 in HIV-infected cells of the patient; and    detecting a resultant decrease in HIV replication at least 48 hr after the increasing step, wherein the amount of HEXIM1 is increased by introducing in the cell an agent that is a hybrid polar compound selected from the group consisting of: hexamethylene bisacetamide (HMBA), suberoylanilide hydroxamic acid (SAHA), m-carboxycinnamic acid bishydroxamide (CBHA), 6-(3-chlorophenylureido)caproic hydroxamic acid (3-Cl-UCHA), diethyl bis-(pentamethylene-N,N-dimethylcarboxamide) malonate (EMBA), suberic bishydroxamic acid (SBHA), suberoyl-3-aminopyridineamide hydroxamic acid (pyroxamide), hexamethylene bis-(3-pyridin) amide (HMBPA), and ethylenediaminetetra acetic acid cobalt (Co-HDTA).    
   
   
       20 . The method of  claim 19  wherein the agent is suberoylanilide hydroxamic acid (SAHA).  
   
   
       21 . The method of  claim 19  wherein the agent is m-carboxycinnamic acid bishydroxamide (CBHA).  
   
   
       22 . The method of  claim 19  wherein the agent is 6-(3-chlorophenylureido)caproic hydroxamic acid (3-Cl-UCHA).  
   
   
       23 . The method of  claim 19  wherein the agent is diethyl bis-(pentamethylene-N,N-dimethylcarboxamide) malonate (EMBA).  
   
   
       24 . The method of  claim 19  wherein the agent is suberic bishydroxamic acid (SBHA).  
   
   
       25 . The method of  claim 19  wherein the agent is suberoyl-3-aminopyridineamide hydroxamic acid (pyroxamide).  
   
   
       26 . The method of  claim 19  wherein the agent is ethylenediaminetetra acetic acid cobalt (Co-HDTA).  
   
   
       27 . The method of  claim 19  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.  
   
   
       28 . The method of  claim 20  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.  
   
   
       29 . The method of  claim 21  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.  
   
   
       30 . The method of  claim 22  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.  
   
   
       31 . The method of  claim 23  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.  
   
   
       32 . The method of  claim 24  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.  
   
   
       33 . The method of  claim 25  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.  
   
   
       34 . The method of  claim 26  wherein the agent is introduced by infusion in the patient, and the resultant decrease in HIV replication is detected at least 72 hr after the increasing step.