Mode of Action

Unique in that Illudofulvenes preferentially block the Transcription-Coupled Repair (TCR) Pathway.

Prior to the discovery of the unusual nature of Illudofulvene cytotoxicity* the only other agent known to produce TCR repairable damage was UV light.

*MJ Kelner, et al. Biochem Pharm 48:403-09, 1994.

The following studies confirm the ability of Illudofulvenes  to damage DNA by a mechanism that can only be repaired by the TCR pathway

Summary

The GGR pathway, responsible for maintaining DNA identity, cannot repair Illudofulvene damage.

  1. This allows Illudofulvene damage to disrupt the TCR pathway and displace the TCR complex.

  2. Upon displacement of the TCR complex, cancer cells undergo apoptosis (cellular suicide).

  3. Non-replicating cells, in contrast, suffer little DNA damage and minimal TCR complex displacement and thereby exhibit a higher tolerance to Illudofulvenes