Methods for identifying metap-2 modulators

A method for identifying MetAP-2 inhibitors suitable for human treatment of disorders, comprising:

• providing a concentration parameter of MetAP-2 selected from the group consisting of IC50, IC90, EC50 as measured at 72 hours in a HUVEC cell, and EC90 as measured at 72 hours in a HUVEC cell;
• exposing HUVEC to a MetAP-2 inhibitor candidate compound at a concentration of about 5 to about 40 times the concentration parameter;
• measuring the inhibition of proliferation in the test cells at 4 hours or at 24 hours;
• and
• selecting the candidate compound as suitable for treatment by identifying whether the candidate compound shows less than or about 15% inhibition of cell proliferation at about 4 hours of exposure to the HUVEC cells.

A method for identifying a candidate MetAP-2 inhibitor compound suitable for human treatment of a disorder, comprising:

• exposing a cell to a potential MetAP-2 compound in a culture medium;
• retrieving a sample from the cell and/or culture medium, at one or more predetermined time points;
• analyzing the sample for increased or decreased expression levels of at least one gene each selected from p53, p21, eNOS, PAI-1, TM, RF, KLF2, MDM2, and vimentin;
• and
• identifying the compound as suitable for treatment to a human patient based on the increased expression level or decreased expression level.

A method for identifying a candidate MetAP-2 inhibitor compound suitable for treatment of a disorder in a human patient, comprising:

• exposing a cell to a potential compound in a culture medium;
• retrieving a sample from the cell and/or culture medium, at one or more predetermined time points;
• analyzing the sample for increased or decreased levels of PAI-1 cell protein;
• and
• identifying the compound as suitable for treatment of a disorder based on the increased or decreased PAI-1 cell protein levels.

A method for identifying MetAP-2 inhibitors having minimal persistant cell proliferation and therefore suitable for human treatment of disorders, comprising:

• exposing test cells or tissue to a MetAP-2 inhibitor candidate compound for a first incubation time;
• performing a washout of the candidate compound from the test cells or tissue after the first incubation time;
• continuing incubation of the cells in the absence of the candidate compound for a second incubation time;
• measuring the inhibition of proliferation in the test cells or tissue in discrete time intervals;
• and
• selecting the candidate compound as suitable for treatment by identifying whether the candidate compound shows minimal inhibition of cell proliferation at a designated time after the washout to the cells or tissue.

A method for identifying a candidate MetAP-2 inhibitor compound suitable for treatment of a disorder in a human patient, comprising:

• exposing a cell or tissue to a potential MetAP-2 inhibitor in a culture medium;
• retrieving a sample from the cell and/or culture medium, at one or more predetermined time points;
• optionally performing a washout of the candidate compound from the test cells or tissue after a first incubation time and continuing incubation;
• analyzing the sample for for increase or decreased gene expression levels and/or increased or decreased protein levels;
• and
• identifying the compound as suitable for treatment of a disorder based on the increased expression level or decreased protein level.