Method of inhibiting apolipoprotein-E expression while increasing expression of at least one of LDL-receptor protein or AbcA1 protein comprising administering a small compound

Patent metadata

Field	Value
Publication number	US-10214502-B2
Application number	US-201615285296-A
Country	US
Kind code	B2
Filing date	Oct 4, 2016
Priority date	Oct 4, 2016
Publication date	Feb 26, 2019
Grant date	Feb 26, 2019

Abstract

This invention offers an effective method of decreasing expression of apolipoprotein E and increasing expression of at least one of either LDL-receptor protein or AbcA1 protein including selecting mammalian cells expressing apoE and at least one of either LDL-receptor protein or AbcA1 protein, contacting the mammalian cell with an effective amount of a compound having general formula (I) or general formula (II) in an amount sufficient to decrease expression of the apoE and increase expression of at least one of the LDL-receptor protein or the AbcA1 protein in the mammalian cell.

First claim

We claim:

1. A method for decreasing expression of apolipoprotein E and increasing expression of at least one of either LDL-receptor protein or AbcA1 protein comprising:
selecting mammalian cells expressing apolipoprotein E and at least one of either LDL-receptor protein or AbcA1 protein;
contacting said mammalian cells with an effective amount of a compound having formula (I) in an amount sufficient to decrease expression of said apolipoprotein E and increase expression of at least one of said LDL-receptor protein or said AbcA1 protein in said mammalian cells:

 wherein Z may be at either position A or position B and may be selected from the group consisting of: CH 2 , CO, or SO 2 , and wherein R 1 may be selected from the group consisting of:

2. A method according to claim 1 , wherein said selecting step selects for mammalian cells expressing apolipoprotein E, LDL-receptor protein, and AbcA1 protein, and wherein said method decreases apolipoprotein E and increases expression of both said LDL-receptor protein and said AbcA1 protein.

3. A method according to claim 1 , wherein said effective amount is 10 μM.

4. A method according to claim 1 , wherein said method decreases expression of apolipoprotein E and increases expression of AbcA1, wherein said Z is located at position A and is SO 2 , and wherein said R 1 is

5. A method according to claim 1 , wherein said method decreases expression of apolipoprotein E and increases expression of LDL-receptor protein, wherein said Z is located at position A and is CH 2 , and wherein said R 1 is

6. A method according to claim 1 , wherein said method decreases expression of apolipoprotein E and increases expression of AbcA1, wherein said Z is located at position A and is CH 2 , and wherein said R 1 is

Assignees

• California State Univ Fresno
• Mayo Found Medical Education & Res

Inventors

• Maitra Santanu
• Kim Jungsu

Classifications

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/18

  Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63) · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K31/5375

  1,4-Oxazines, e.g. morpholine · CPC title