Compounds and methods of identifying, synthesizing, optimizing and profiling protein modulators

A method of testing cellular specificity of a chemical agent, the method comprising:

• a) providing a test cell which expresses a target protein and is capable of manifesting a phenoresponse linked to the presence and functional activity of the target protein in the cell and wherein the phenoresponse is also capable of being modulated by a known modulator;
• b) providing a control cell which expresses the target protein at a lower level than the test cell or does not express the target protein, the control cell being capable of manifesting the phenoresponse to a lesser extent than the test cell or not at all;
• c) measuring modulation of the phenoresponse of the test cell treated with the known modulator;
• d) measuring modulation of the phenoresponse of the control cell treated with the known modulator;
• e) measuring modulation of the phenoresponse of the test cell treated with a chemical agent;
• f) measuring modulation of the phenoresponse of the control cell treated with the chemical agent;
• g) determining the cellular specificity of the chemical agent using the test cell and the control cell, and the cellular specificity of the known modulator using the test cell and the control cell;
• h) comparing the cellular specificity of the chemical agent to the cellular specificity of the known modulator and, if the cellular specificity of the chemical agent is greater than the cellular specificity of the known modulator, determining that the cellular specificity of the chemical agent is improved compared to the cellular specificity of the known modulator.