Modulators of RabGGT and methods of use thereof

A method of inhibiting tumor growth in an individual having a tumor, the method comprising:

• identifying a compound that is a RabGGT inhibitor;
• testing the ability of the compound to modulate farnesyl transferase (FT) activity;
• modifying the compound, wherein the modified compound exhibits reduced modulation of FT activity compared to the unmodified compound, wherein inhibition of RabGGT is retained;
• and
• administering to the individual an effective amount of an agent that is a RabGGT inhibitor.

A method of identifying an agent that selectively modulates RabGGT enzymatic activity, the method comprising;

• determining the effect, if any, of the agent on enzymatic activity of RabGGT;
• and
• determining the effect, if any, of the agent on enzymatic activity of farnesyl transferase;
• wherein an increase or decrease of enzymatic activity of RabGGT of at least about 15% compared to the enzymatic activity of RabGGT in the absence of the agent, and a reduction of enzymatic activity of farnesyl transferase of less than about 10% compared to the enzymatic activity of famesyl transferase in the absence of the agent, indicates that the agent is a selective modulator of RabGGT enzymatic activity.

A method of identifying an agent that modulates RabGGT enzymatic activity and modulates apoptosis, the method comprising:

• determining the effect, if any, of the agent on RabGGT enzymatic activity;
• and
• determining the effect, if any, of the agent on apoptosis in a eukaryotic cell,
• wherein an increase or decrease of enzymatic activity of RabGGT of at least about 15% compared to the enzymatic activity of RabGGT in the absence of the agent, and wherein an increase or decrease in apoptosis of at least about 15% compared to the level of apoptosis in the absence of the agent indicates that the agent modulates RabGGT enzymatic activity and apoptosis.

A computer for producing a three-dimensional representation of a RabGGT protein, wherein said computer comprises:

• a machine-readable data storage medium comprising a data storage material encoded with machine-readable data, wherein said data comprises the three-dimensional coordinates of a subset of the atoms in RabGGT polypeptide;
• a working memory for storing instructions for processing said machine-readable data;
• a central-processing unit coupled to said working memory and to said machine-readable data storage medium for processing said machine readable data into said three-dimensional representation;
• and
• a display coupled to said central-processing unit for displaying said three-dimensional representation.

A computer-assisted method for identifying potential modulators of apoptosis, using a programmed computer comprising a processor, a data storage system, an input device, and an output device, comprising the steps of:

• (a) inputting into the programmed computer through said input device data comprising the three-dimensional coordinates of a subset of the atoms in a RabGGT enzyme, thereby generating a criteria data set;
• (b) comparing, using said processor, said criteria data set to a computer database of chemical structures stored in said computer data storage system;
• (c) selecting from said database, using computer methods, chemical structures having a portion that is structurally similar to said criteria data set;
• (d) outputting to said output device the selected chemical structures having a portion similar to said criteria data set.