Modulators of 14-3-3 functionality and uses thereof
The present disclosure relates to modulators of 14-3-3 functionality and their use in methods and compositions for preventing and/or treating various diseases, conditions and states, such as cancer and healing of wounds. Certain embodiments of the present disclosure provide a method of preventing and/or treating a disease, condition or state in a subject associated with altered 14-3-3 protein functionality and/or which would benefit from altering 14-3-3 functionality, the method comprising administering to the subject an effective amount of an agent which inhibits dimerization of the 14-3-3 protein, thereby preventing and/or treating the disease, condition or state in the subject.
1. A method of treating a disease, condition or state in a human subject associated with increased 14-3-3 protein functionality, wherein the disease, condition or state is a lung cancer, a leukemia or a wound, the method comprising administering to the human subject an effective amount of an agent which inhibits dimerization of the 14-3-3 protein, wherein the agent comprises a compound of the following formula:
and/or
and/or a pharmaceutically acceptable salt or solvate thereof, thereby treating the disease, condition or state in the subject.
2. The method according to claim 1 , wherein the agent is administered to the subject at a concentration of 0.5-50 mg/kg body weight.
3. The method according to claim 1 , wherein the disease, condition or state is a lung cancer or a leukemia and the method further comprises administration of an anti-cancer agent.
4. The method according to claim 1 , wherein the disease, condition or state comprises a wound and the administering of the agent comprises topical administration to the wound.
5. The method according to claim 4 , wherein the subject is suffering from, or susceptible to, diabetes.
6. The method according to claim 1 , wherein the lung cancer is non-small cell lung cancer.
7. The method according to claim 1 , wherein the leukemia is T-cell leukemia.