The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18;257:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid memb...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils
In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results s...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Abid Ali Kiryl Zhaliazka Tianyi Dou Aidan P Holman Dmitry Kurouski Source Type: research
The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18;257:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid memb...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils
In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results s...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Abid Ali Kiryl Zhaliazka Tianyi Dou Aidan P Holman Dmitry Kurouski Source Type: research
The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18;257:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid memb...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils
In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results s...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Abid Ali Kiryl Zhaliazka Tianyi Dou Aidan P Holman Dmitry Kurouski Source Type: research
The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18;257:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid memb...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils
In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results s...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Abid Ali Kiryl Zhaliazka Tianyi Dou Aidan P Holman Dmitry Kurouski Source Type: research
The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18;257:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid memb...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils
In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results s...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Abid Ali Kiryl Zhaliazka Tianyi Dou Aidan P Holman Dmitry Kurouski Source Type: research
The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18;257:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid memb...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils
In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results s...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Abid Ali Kiryl Zhaliazka Tianyi Dou Aidan P Holman Dmitry Kurouski Source Type: research
The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18;257:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid memb...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils
In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results s...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Abid Ali Kiryl Zhaliazka Tianyi Dou Aidan P Holman Dmitry Kurouski Source Type: research
The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study
Chem Phys Lipids. 2023 Oct 18:105351. doi: 10.1016/j.chemphyslip.2023.105351. Online ahead of print.ABSTRACTCeritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid membrane...
Source: Chemistry and Physics of Lipids - October 20, 2023 Category: Lipidology Authors: Markus Fischer Meike Luck Max Werle Alexander Vogel Mohammad Bashawat Kai Ludwig Holger A Scheidt Peter M üller Source Type: research
