# US 2013/0158098 A1 · Alkenyl Substituted Cycloaliphatic Compounds as Chemical Inducers of Proximity

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- Number: US 2013/0158098 A1
- Document ID: US20130158098A1
- Status: Published application
- Kind: A1
- Application number: 13/704,517
- Filed: 2011-06-15
- Published: 2013-06-20
- Earliest claimed: 2010-06-21
- Assignees: The Board of Trustees of the Leland Standford Junior University
- Inventors: Fu-Sen Liang; Gerald R. Crabtree
- Web page: https://patentgrep.com/patent/US20130158098A1

## CPC

- A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- C12N 5/0602: {Vertebrate cells}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Methods of inducing proximity of chimeric molecules in a cell are provided. Aspects of the methods include contacting a cell with an amount of alkenyl substituted cycloaliphatic (ASC) inducer compound, e.g., abscisic acid, effective to induce proximity of first and second chimeric molecules. Also provided are compositions and kits for practicing various embodiments of the methods. Methods of the invention find use in a variety of different applications, including transcription induction applications.

## Claims

### Claim 1

A method of inducing proximity of first and second chimeric molecules in a cell, the method comprising:
contacting the cell with an amount of an alkenyl substituted cycloaliphatic (ASC) inducer compound effective to induce proximity of the first and second chimeric molecules, wherein the first and second chimeric molecules each comprise an ASC inducer domain and an effector domain.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the ASC inducer compound comprises a cycloaliphatic ring substituted with a hydroxyl and/or oxo group.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the ASC inducer compound is described by the formula:
wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from hydrogen, an alkyl, an aryl, an alkenyl, an alkynyl, a carbonyl, an acyl, a halogen, a hydroxy, an alkoxy, an aryloxy, and a heterocyclic group and any two of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 can optionally be cyclically linked.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the ASC inducer compound is abscisic acid.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the first and second chimeric molecules are chimeric proteins.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the ASC inducer domain of the first chimeric protein is an ASC inducer compound specific binding domain.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the ASC inducer compound specific binding domain of the first chimeric protein comprises a PYR abscisic acid binding domain.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the effector domains of the first and second chimeric molecules are different.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the effector domain of the first chimeric molecule is a DNA binding domain and the effector domain of the second chimeric molecule is a transcription activation domain.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the effector domain of the first chimeric molecule is a cellular localization domain and the effector domain of the second chimeric molecule is a member of a signaling pathway.

### Claim 11

A nucleic acid comprising a coding sequence for a chimeric protein that comprises ASC inducer domain and an effector domain.

### Claim 12 (depends on 11)

The nucleic acid according to claim 11, wherein the ASC inducer domain is an abscisic acid specific binding domain.

### Claim 13

A kit comprising:
first and second nucleic acids each encoding a chimeric protein that comprises an ASC inducer domain and an effector domain; and
an ASC inducer compound.

### Claim 14

A composition comprising:
an ASC inducer compound; and
a pharmaceutically acceptable vehicle.

### Claim at position 15

15-16. (canceled)

### Claim 17 (depends on 14)

The composition according to claim 14, wherein the ASC inducer compound comprises a cycloaliphatic ring substituted with a hydroxyl and/or oxo group.

### Claim 18 (depends on 17)

The composition according to claim 17, wherein the ASC inducer compound is described by the formula:
wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from hydrogen, an alkyl, an aryl, an alkenyl, an alkynyl, a carbonyl, an acyl, a halogen, a hydroxy, an alkoxy, an aryloxy, and a heterocyclic group and any two of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 can optionally be cyclically linked.

### Claim 19 (depends on 18)

The composition according to claim 18, wherein the ASC inducer compound is abscisic acid.