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The initial focus is on inhibitors of plasma kallikrein, which is an important component of the body's inflammatory response and which, in excess, can lead to increased vascular permeability, edema, and inflammation.
Pharmacodynamic assessments showed that lanadelumab inhibited kallikrein in a linear, dose-dependent manner, and the two higher doses reduced levels of cleaved high-molecular-weight kininogen to those reported in healthy controls.
The qPCR measurements were used to evaluate the impact of elevated miR-375 expression on the mRNA expression of the commonly regulated proteases, kallikrein 6 (KLK6), kallikrein 10 (KLK10), and matrix metalloproteinase 9 (MMP9).
The poster, titled "Discovery and characterization of a fully human monoclonal antibody inhibitor of plasma kallikrein for the treatment of plasma kallikrein-mediated edema," (poster #116) highlighted results of preclinical work that was designed to evaluate the activity of DX-2930 as a long-acting inhibitor of plasma kallikrein (pKal).
Further studies by the Joslin researchers showed that normalizing blood glucose levels in diabetic animals could block the effect from plasma kallikrein, and that rapidly inducing hyperglycemia in control animals mimicked the effects of diabetes on brain hemorrhage.
Evaluation of kallikrein in human parotid and submandibular saliva.
1]-proteinase inhibitor and tissue kallikrein in controlling allergic ovine airway hyperresponsiveness.
The condition is caused by a genetic deficiency of C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits kallikrein and other serine proteases in the blood.
Activation of the zymogen form of prostate-specific antigen by human glandular kallikrein 2.
PSA and human kallikrein 2 are closely related products of human kallikrein genes KLK3 and KLK2, respectively.
A well-known example of a kallikrein is PSA (hK3), which is used in diagnosing prostate cancer.
Issued to Calydon are United States Patent 6,057,299, United States Patent 6,051,417 and United States Patent 6,136,792 that cover two human prostate-specific transcriptional regulatory sequences: a human prostate-specific antigen enhancer; and a human glandular kallikrein enhancer.