Methods to identify compounds useful for the treatment of proliferative and differentiative disorders

A method for screening compounds that modulate Fbp1-related disorders, comprising:

• a) contacting a compound with a cell or a cell extract expressing Fbp1 and Fbp5, and detecting a change in the activity of Fbp1, and
• b) measuring the level of Fbp1 activity in a cell or cell extract in the absence of said compound,
• such that if the level of Fbp1 activity measured in (b) differs from the level of activity in (a), then a compound that modulates an Fbp1-related disorder is identified.

A method for screening compounds useful for the treatment of proliferative and differentiative disorders comprising contacting a compound with a cell or a cell extract expressing both Fbp1 and βTrcp2, and an Fbp1 target substrate, and detecting a change in the activity of Fbp1 or βTrcp2.

A method for screening compounds useful for the treatment of proliferative and differentiative disorders comprising:

• a) contacting a compound with a cell or a cell extract expressing Fbp1, and a test compound, and detecting a change in the activity of Fbp1, and
• b) contacting a compound with a cell or a cell extract expressing βTrcp2, and a test compound, and detecting a change in the activity of βTrcp2, and
• c) contacting a compound with a cell or a cell extract expressing Fbp1 and βTrcp2, and the test compound or compounds identified as changing the activity of Fbp1 or βTrcp2, and detecting a change in the activity of Fbp1 or βTrcp2.

A method for diagnosing decreased fertility by examining Fbp1 in infertile individuals, comprising:

• a) measuring the level of Fbp1 expression or activity in a tissue sample from an affected individual, and
• b) comparing the level of Fbp1 expression or activity in the affected individual with the level of Fbp1 expression or activity in a clinically normal individual,
• such that if decreased levels of Fbp1 expression or activity are detected in the affected individual relative to the clinically normal individual, an Fbp1-related infertility disorder is diagnosed.

A pharmaceutical composition for the treatment of Fb p1-related infertility, comprising (a) a compound that modulates Fbp1 activity and (b) a pharmaceutically acceptable carrier.

A method of treating Fbp1-related infertility, comprising administering to an individual in the need of such treatment a compound that modulates Fbp1 activity, in an amount effective for the treatment of the infertility.

A method for detecting an Fbp1-related infertility disorder in a mammal comprising measuring the level of Fbp1 activity or expression in said mammal, such that if the measured Fbp1 activity or expression differs from the level found in clinically normal individuals, then a Fbp1-related infertility disorder is detected.