Small organic molecule regulators of cell proliferation

• US 20080182859A1
• Filed: 11/02/2007
• Published: 07/31/2008
• Est. Priority Date: 11/02/2006
• Status: Abandoned Application

• Current Assignee: Curis, Inc.
• Original Assignee: Curis, Inc.
• Inventors: Kruse, Lawrence I., Guicherit, Oivin M., Brunton, Shirley Ann
• Application Number:
  US11/982,718
• Publication Number:
  US 20080182859A1
• Time in Patent Office: Days
• US Class Current: 514/255.05
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 333/70 attached in position 2
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a compound. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal patched pathway or agonizing smoothened or hedgehog activity.

Claims

1. A compound selected from:

2. A composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient;

wherein the composition is optionally suitable for oral or topical administration.

3. A method for

A) agonizing the hedgehog pathway in a cell, comprising contacting the cell with a compound of claim 1 or a composition of claim 2;

wherein the method is optionally characterized by one or more of the following;

the cell is contacted with the compound in vitro;

or

the cell is contacted with the compound in vivo;

or

B) modulating proliferation, differentiation, or survival of a cell, comprising contacting the cell with a compound of claim 1 or a composition of claim 2;

wherein the method is optionally characterized by one or more of the following;

the cell is contacted with the compound in vitro;

or

the cell is contacted with the compound in vivo;

or

C) treating or preventing cardiovascular disease, comprising administering a compound of claim 1 or a composition of claim 2 to a patient in need thereof;

wherein the compound or composition is optionally released from a stent;

wherein the stent optionally releases the compound or composition over a period of at least about 4, 8, 12, 24, 48, or 72 hours, at least about 1, 2, 3, 4, or 5 days, at least about 1, 2, or 3 weeks, or at least about 1, 2, 3, 4, 5, or 6 months;

or

D) promoting angiogenesis, comprising administering a compound of claim 1 or a composition of claim 2;

or

E) growing or culturing cells in vitro, comprising contacting the cells with a compound of claim 1 or a composition of claim 2;

wherein the method is optionally characterized by one or more of the following;

the cells are progenitor cells;

the cells are neural progenitor cells;

or

the cells are neuronal cells;

or

F) delivering cells to an anatomical site of a patient, comprising;

culturing the cells, including contacting the cells with a compound of a claim 1 or a composition of claim 2; and

implanting the cells at the anatomical site of the patient;

wherein the cells are neuronal cells;

or

G) promoting wound healing, comprising administering-to a patient a compound of claim 1 or a composition of claim 2;

or

H) inhibiting aging effects on skin, comprising administering to a patient a compound of claim 1 or a composition of claim 2;

or

I) regulating skin or hair growth, comprising administering to a patient a compound of claim 1 or a composition of claim 2;

J) promoting the formation and/or proliferation of hair follicles, comprising administering a compound of claim 1 or a composition of claim 2;

wherein the method is optionally characterized by one or more of the following;

the compound or composition is administered to a patient;

or

the method is an ex vivo method;

or

K) increasing hair coverage at an anatomical site of a patient, comprising

a) growing hair by ex vivo culture, formation, growth, differentiation, and/or expansion of hair follicles comprising contacting cells with a compound of claim 1 or a composition of claim 2; and

b) implanting the grown hair at the anatomical site of the patient;

or

L) inducing anagen in a telogenic hair follicle, comprising administering a compound of claim 1 or a composition of claim 2;

wherein the method is optionally characterized by one or more of the following;

the compound or composition is administered to a patient;

or

the method is an ex vivo method;

or

M) increasing the trichogenicity of hair follicle cells, comprising contacting the cells with a compound of claim 1 or a composition of claim 2;

wherein the method is optionally characterized by one or more of the following;

the compound or composition is administered to a patient;

or

the method is an ex vivo method;

or

N) treating or preventing alopecia in a patient comprising administering a compound of any one of claim 1 or a composition of claim 2;

wherein the method is optionally characterized by one or more of the following;

the alopecia is alopecia areata;

or

the alopecia is alopecia totalis;

wherein in any of the methods described in sections I) to N) above the patient optionally displays male or female pattern baldness;

wherein in any of the methods described in sections G) to N) above the compound or composition is optionally administered topically;

wherein in any of the methods described in sections G) to N) above the patient is optionally a human;

wherein in any of the methods described in sections G) to N) above the patient is optionally a non-human animal;

wherein the patient is optionally a dog;

or

O) treating or preventing amyotrophic lateral sclerosis (ALS), comprising administering a compound of claim 1 or a composition of claim 2;

or

P) treating or preventing multiple sclerosis (MS), comprising administering a compound of any one of claim 1 or a composition of claim 2;

or

Q) treating or preventing Parkinson'"'"'s disease or Huntington'"'"'s disease, comprising administering a compound of claim 1 or a composition of claim 2.