Characterization of binding mode of imatinib to human α1-acid glycoprotein

Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib

“…Like SA, AGP has also been reported to bind to Imatinib, thus negatively influencing its therapeutic activity in cancer patients ( Kremer et al, 1988; Gambacorti-Passerini et al, 2000; Fitos et al, 2006, 2012; Hegde et al, 2012 ). To investigate the effect of AGP in our system, adult S. mansoni couples were maintained in culture medium, which was supplemented with human AGP at a final concentration of 0.8 g/L, similar to that found in human plasma (0.5–1.4 g/L) ( Schultz and Arnold, 1990; Gambacorti-Passerini et al, 2000 ).…”

“…To answer the question why the in vivo studies using Imatinib in the mouse and hamster models failed, we focused on SA and AGP as they are known to bind to drugs negatively influencing their action ( Piafsky, 1980; Kremer et al, 1988; Svensson et al, 1986 ). This includes Imatinib, which was reported to be bound by both of these major blood components ( Gambacorti-Passerini et al, 2000; Fitos et al, 2006, 2012; Hegde et al, 2012 ). Whereas no evidence was reported for a negative influence of HSA for Imatinib activity ( Hegde et al, 2012 ), there are controversial opinions about the consequences of its interaction with AGP.…”

Imatinib binding to human serum albumin modulates heme association and reactivity

“…This study reports a detailed functional and structural characterization of imatinib binding to HSA, which may act as the secondary carrier of the drug in pathological states characterized by low plasma levels of AGP [20]; indeed AGP represents the first carrier of imatinib [7][8][9][10][11]13,66]. Moreover, the modulation of heme-Fe(III) binding to HSA and the reactivity of HSA-heme-Fe(III) by imatinib has been deeply investigated.…”

Molecular Aspects of Human Alpha-1 Acid Glycoprotein — Structure and Function

“…[75] In addition to these drugs, molecular docking models of imatinib, 6-mercaptopurine and thymoquinone, -AGP variants complex have also been developed. [76][77][78] CD and fluorescence spectrometry is also a useful tool for examining the drug-binding sites of AGP. We found that electrostatic and hydrophobic forces have an important role in interactions between AGP and basic drugs.…”