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Updated: Jul 8, 2026

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
Published on: March 17, 2010
Pharmacokinetic Parameters of Recombinant Human Cyclophilin A in Mice
Anastasiia Kalinina1, Elena Grigorieva1, Anna Smirnova1
1Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Kashirskoe sh. 24, 115478, Moscow, Russian Federation.
Background And Objective:
Cyclophilin A (CypA) is an isomerase that functions as a chaperone, housekeeping protein, and cyclosporine A (CsA) ligand. Secreted CypA is a proinflammatory factor, chemoattractant, immune regulator, and factor of antitumor immunity. Experimental data suggest clinical applications of recombinant human CypA (rhCypA) as a biotherapeutic for cancer immunotherapy, stimulation of tissue regeneration, treatment of brain pathologies, and as a supportive treatment for CsA-based therapies. The objective of this study is to analyze the pharmacokinetics of rhCypA in a mouse model.
Methods:
rhCypA was isotope-labeled with 125I and injected intraperitoneally (i.p.) or subcutaneously (s/c) into female mice as a single dose of 100 μg per mouse, equivalent to the estimated first-in-human dose. Analysis of 125I-rhCypA biodistribution and excretion was performed by direct radiometry of the blood, viscera, and urine of mice 0.5-72 h following its administration.
Results:
rhCypA showed rapid and even tissue-organ distribution, with the highest tropism (fT = 1.56) and accumulation (maximum concentration, Cmax = 137-167 μg/g) in the kidneys, its primary excretory organ. rhCypA showed the lowest tropism to the bone marrow and the brain (fT = 0.07) but the longest retention in these organs [mean retention time (MRT) = 25-28 h].
Conclusion:
This study identified promising target organs for rhCypA's potential therapeutic effects. The mode of rhCypA accumulation and retention in organs could be primarily due to the expression of its receptors in them. For the first time, rhCypA was shown to cross the blood-brain barrier and accumulate in the brain. These rhCypA pharmacokinetic data could be extrapolated to humans as preliminary data for possible clinical trials.
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