Orally active peptidic bradykinin B1 receptor antagonists engineered from a cyclotide scaffold for inflammatory pain treatment

Article abstract of DOI:10.1002/anie.201200984

Edible: By grafting natural peptide antagonists onto the cyclotide kalata B1, orally active peptides were engineered, which are potentially useful therapeutics for the treatment of inflammatory pain. For example, the entire loop 6 of kalata B1 was replaced with the peptidic bradykinin B₁ receptor antagonist DALK (red in scheme) to obtain the cyclic bradykinin antagonist ckb-kal. Copyright

Full text of DOI:10.1002/anie.201200984

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Indication
Neurology
Pain
Target/marker/pathway Summary
Licensing status information
Bradykinin B1 receptor
(BDKRB1; B1R)
An in vitro and mouse study identified cyclic
peptide–based B1R antagonists that could
help treat pain. e antagonists were created
by linking known peptide inhibitors of B1R to
kalata B1, an orally available cysteine-rich plant
peptide with a cyclic backbone. In a mouse
model of visceral pain, oral dosing of the new
antagonists decreased pain compared with
dosing of the linear parent peptides. Next steps
include determining the bioavailability of the new
inhibitors in small animals.
Patent application
filed; available for
licensing
Wong, C.T.T. et al. Angew. Chem. Int.
Ed.; published online April 24, 2012;
doi:10.1002/anie.201200984
Contact: James P. Tam, Nanyang
Technological University, Singapore,
Singapore
e-mail:
jptam@ntu.edu.sg
Evotec AG has a B1R antagonist in preclinical
development for pain and inflammation.
SciBX 5(20); doi:10.1038/scibx.2012.527
Published online May 17, 2012
SciBX: Science–Business eXchange
Copyright © 2012 Nature Publishing Group
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