The company's principal technology centres on the rational chemical modification of members of a group of naturally occurring antitumour antibiotics known as the pyrrolobenzodiazepines (or “PBDs” for short). These molecules have the useful characteristic of specifically targeting guanine bases in double-stranded helical DNA. The company has built-up substantial synthetic and Structure Activity Relationship (SAR) expertises for the PBDs and can now manipulate PBD-based molecules to target not just the guanine base but also a number of flanking base sequences with a high degree of selectivity. Spirogen also has a complementary technology based on the duocarmycins, a different family of antitumour antibiotics, which target adenine bases. These technologies have been used by the company to design and develop a pipeline of PBD-based, discrete, single-agent anticancer drugs (with one about to enter Phase II), and also to develop small-molecule “gene targeting” agents potentially capable of down-regulating single genes or sets of genes by blocking transcription in the coding regions of genes or by selectively inhibiting transcription factor binding. Agents of this type are viewed as a small-molecule equivalent of macromolecular gene silencing technologies such as antisense and RNAi, but with all the benefits of small drug-like molecules—such as ease of manufacture, and good pharmacokinetic and cell/nucleus permeability properties. These agents are being developed as research tools, and also as potential therapeutic agents in cancer and infectious diseases where clear guest/host genetic differences are established.
