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Name

Highly Effective Chemoprotective and Radioprotective Drugs from DKFZ Heidelberg

Organization name

DKFZ Deutsches Krebsforschungszentrum

Profile

Key facts

  • Chemo/radiotherapy-induced side effects limit the applicable doses during cancer treatment
  • Rocaglamide A (Roc-A) and derivatives show chemo- and radioprotective efficacy in highly proliferating cells like hematopoietic progenitor cells, in slowly proliferating cells like cardiomyocytes and in quiescent cells like T and B cells.
  • Roc-A and derivatives are highly specific for normal cells and do not protect p53-deficient/mutated cancer cells
  • Roc-A has a wide therapeutic window and is highly potent (nM range)

Abstract

The efficacy of chemo- and radiotherapy is limited by adverse side effects like neutropenia. Reducing these side effects would allow dose escalation and would therefore lead to a more efficient eradication of the tumor by radiation and chemotherapeutics. Only a few chemo/radioprotective drugs are clinically available. Moreover, the majority of drugs have major drawbacks. For instance, the only FDA-approved radioprotective drug Amifostine (Ethyol®) is unspecific in many therapeutic settings and exerts its effects only at micromolar concentrations. The current technology provides Rocaglamide A (RocA) and other derivatives as specific and highly potent chemo/radioprotective drugs with a wide therapeutic window.

Development Stage

In in vitro assays the chemoprotective efficacy of Roc-A was tested by 8-fold increased exposure of malignant and non-malignant cells to Etoposide. Increasing the Etoposide dose led to a 3-fold increase in cell death. With the co-application of Roc-A, non-malignant cells were not affected by the Etoposide dose increase. Similar results were obtained for ionizing radiation. In vivo experiments are ongoing.

The Technology

The chemoprotective and radioprotective potential of Roc-A is based on the fact that Roc-A prevents the death of healthy cells by inhibiting p53 expression at the translational level (see Reference).

Applications and Commercial Opportunity

DKFZ is looking for a licensing or collaboration partner for its technology to further develop these promising chemo/radioprotective drugs.

Inventors

The inventors are Min Li-Weber, Michael S. Becker and Peter H. Krammer, all employees of DKFZ.

Intellectual Property

A European patent application was filed in November 2013.

Reference

Becker et al. “The traditional Chinese medical compound Rocaglamide protects nonmalignant primary cells from DNA damage-induced toxicity by inhibition of p53 expression”, Cell Death Dis. (2014); 5:e1000.

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