Use of bisindolylmaleimide compounds to induce Fas-mediated apoptosis

A method for inducing apoptosis in a target cell of a subject, said method comprising administering to the subject a pharmaceutically effective amount of at least one compound of the formula:

• wherein:
• R1 is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, C3-C7 heterocycle, or C3-C7 substituted heterocycle;
• R2 and R3 are independently H or C1-C12 alkyl;
• and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, wherein following said administering step, the target cell is caused to undergo apoptosis, wherein R1 is C3-C7-heterocycle.

A method for inducing apoptosis in a target cell of a subject, said method comprising administering to the subject a pharmaceutically effective amount of at least one compound of the formula:

• wherein:
• R1 is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, C3-C7 heterocycle, or C3-C7 substituted heterocycle;
• R2 and R3 are independently H or C1-C12 alkyl;
• and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, wherein following said administering step, the target cell is caused to undergo apoptosis, wherein the target cell is a lymphocyte.

A method for treating a subject having a T cell mediated autoimmune disorder, said method comprising administering to a subject having a T cell mediated autoimmune disorder characterized by defective or insufficient activation-induced cell death of activated autoreactive T cells, a pharmaceutically effective amount of at least one compound of the formula:

• wherein:
• R1 is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, C3-C7 heterocycle, or —C3-C7 substituted heterocycle;
• R2 and R3 are independently H or C1-C12 alkyl;
• and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, wherein administration of the at least one compound of formula I causes activation-induced cell death of the activated autoreactive T cells.

A method for preventing T cell tolerance in a subject, said method comprising eliminating activated T cells having impaired apoptosis by administering a pharmaceutically effective amount of at least one compound of the formula:

• wherein:
• R1 is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, C3-C7 heterocycle, or C3-C7 substituted heterocycle;
• R2 and R3 are independently H or C1-C12 alkyl;
• and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, wherein following said administering step, the activated T cells having impaired apoptosis are caused to undergo apoptosis.

A method for facilitating Fas-mediated intracellular signaling in a cell, said method comprising administering to the cell a pharmaceutically effective amount of at least one compound of a formula:

• wherein:
• R1 is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, C3-C7 heterocycle, or —C3-C7 substituted heterocycle;
• R 2 and R3 are independently H or C1-C12 alkyl;
• and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.

A method for inhibiting Fas-induced production of bcl-2 anti-apoptotic protein, said method comprising administering to the subject a pharmaceutically effective amount of at least one compound of the formula:

• wherein:
• R1 is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, C3-C7 heterocycle, or C3-C7 substituted heterocycle;
• R2 and R3 are independently H or C1-C12 alkyl;
• and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.