ReviewMolecular and pharmacodynamic characteristics of the novel multi-target tumor growth inhibitor ZK 304709
Introduction
The majority of human solid tumors especially those derived from the gastrointestinal tract, breast, and lung cannot be cured if metastases occurred. Chemotherapy, radiation therapy, antibody therapies and anti angiogenic therapy have a certain positive influence on survival, but there is plenty of room for clinical improvement.
This may be achieved by compounds having a novel mode of action. Here we present the novel development compound ZK 304709 having a mode of action different from standard chemotherapy and showing strong anti tumor efficacy in a variety of standard human xeno-transplantation models as well as orthotopic models for pancreatic carcinoma.
Section snippets
Results and discussion
ZK 304709 is a first-in-class, oral multi-target tumor growth inhibitor™ (MTGI™) that blocks tumor cell proliferation and induces apoptosis by inhibiting a unique combination of disease progression driving pathways. This is accomplished by potent inhibition of (a) serine/threonine kinases CDK 1, 2 and 4 leading to inhibition of cell cycle progression, (b) serine/threonine kinases CDK 7 and 9 leading to apoptosis in resting tumor cells, (c) receptor tyrosine kinases VEGF-R1, R2 and R3, and
Conclusion
The combined inhibition of cell cycle and angiogenesis by ZK 304709 resulted in superior efficacy compared to standard chemotherapeutic compounds both in s.c. human tumor xenografts as well as orthotopic human pancreatic carcinoma models. ZK 304709 is in Phase I clinical studies.
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