Breaking into Merck’s CCK Patents: the Starting
Point of PNB Vesper Life Science to Design and
Develop Cholecystokinin(CCK)-Antagonists as
Targeted Chemotherapeutics
Volume 1 - Issue 2
Eric Lattmann*1 and Pornthip Lattmann2
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- 1School of Life and Health Sciences, Aston University, England
- 2PNB Vesper Life Science PVT, India
*Corresponding author:
Eric Lattmann, Aston School of Pharmacy, Aston University,
England
Received: March 23, 2018; Published: March 29, 2018
DOI: 10.32474/DDIPIJ.2018.01.000106
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Abstract
Early anti-cancer research was dominated by the development of alkylating agents, followed by the discovery of a variety of
anti-metabolites, which were useful anti-viral agents at the same time. Current anti-cancer drugs are designed towards molecular
targets in order to reduce their toxicity and to enhance the selectivity on the cancer cells. Within an increasingly growing number
of molecular targets, the cholecystokinin, as a neuro modulator, became an important anti-cancer target, especially when it was
shown that cholecystokinin regulates the invasiveness of human pancreatic cancer cell lines via the protein kinase C pathway. The
low potency and the lack of subtype receptor selectivity of those early non-peptide CCK-antagonists, was improved in the following
generations of CCK antagonists. These potent and selective antagonists have shown disappointing results in clinical trials due to a
poor bioavailability. Initially cholecystokinin was discussed as growth factor, not only in pancreatic cancer, but also for lung, breast,
colon and brain cancer, followed by a detailed discussion of over 20 different chemical classes having been developed to date, mainly
for the area of neuroscience. Loxiglumide, CI-988, Devazepide, L-365,260 and YM022 are highlighted including in vivo studies and
clinical trials. Moreover, CCK antagonists were found useful in the enhancement of the analgesic effects of morphine and the anti-neo
plastic effect of cis-platinium. Clinical trials are ongoing. It is concluded that non peptidal cholecystokinin receptor antagonists are
modern, non-toxic anti-cancer agents.
Abbrevations: GI: Gastrointestinal: Bt2cGMP:Dibutyryl Cyclic Guanosine Mono Phosphate; Bt2cGMP:Dibutyryl Cyclic Guanosine
Mono Phosphate; CCK: Cholecystokinin
Abstract|
Introduction|
Cholecystokinin and Cancers|
From CNS Drugs to New Anticancer Agents|
Amino Acid Derivatives|
Loxiglumide and Proglumide as Early Anti-Cancer
Agents|
Evaluation of CI-988 as Anti-Cancer Agent|
Benzodiazepine Derivatives|
Ureidobenzodiazepine Derivatives|
Recent Clinical Studies|
Potentiation of Clinical Effects|
Conclusion|
References|