Patent ID: 7390629

Claim:
A method for identifying a tumor-activated prodrug-form of a therapeutic agent, the therapeutic agent having desired activity in a tumor cell which secrets an enzyme secreted by MCF7/6, HepG2, or HT29 cells, wherein the tumor-activated prodrug is capable of providing the therapeutic agent selectively to the tumor cell in the presence of a normal cell, the method comprising: (a) identifying a substrate of an enzyme that is secreted by MCF7/6, HepG2, or HT29 cells, wherein the enzyme is not secreted by normal cells; (b) covalently attaching the substrate to the therapeutic agent to form a prospective tumor-activated prodrug; (c) testing to determine: (i) whether the enzyme cleaves the prospective tumor-activated prodrug into fragments when the prospective tumor-activated prodrug contacts an extracellular medium surrounding the tumor cell, one of the fragments being referred to as a prospective active fragment; (ii) whether the prospective active fragment enters the tumor cell from the extracellular medium; (iii) whether the prospective active fragment is active in the tumor cell, in which case the prospective active fragment is referred to as an active fragment; (iv) whether the prospective tumor-activated prodrug enters the normal cell; (d) identifying as a tumor-activated prodrug any prospective tumor-activated prodrug that meets the following conditions: (i) cleavage by the enzyme produces a prospective active fragment when the prospective tumor-active prodrug contacts the extracellular medium surrounding the tumor cell; (ii) the prospective active fragment enters the tumor cell; (iii) the prospective active fragment is an active fragment; (iv) the prospective tumor-activated prodrug does not enter the normal cell.