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Characterization of midostaurin as a dual inhibitor of FLT3 and SYK and potentiation of FLT3 inhibition against FLT3-ITD-driven leukemia harboring activated SYK kinase.

Oncotarget

Weisberg EL, Puissant A, Stone R, Sattler M, Buhrlage SJ, Yang J, Manley PW, Meng C, Buonopane M, Daley JF, Lazo S, Wright R, Weinstock DM, Christie AL, Stegmaier K, Griffin JD.
PMID: 28881711
Oncotarget. 2017 Jul 06;8(32):52026-52044. doi: 10.18632/oncotarget.19036. eCollection 2017 Aug 08.

Oncogenic FLT3 kinase is a clinically validated target in acute myeloid leukemia (AML), and both multi-targeted and selective FLT3 inhibitors have been developed. Spleen tyrosine kinase (SYK) has been shown to be activated and increased in FLT3-ITD-positive AML patients,...

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Weisberg EL, Puissant A, Stone R, et al. Characterization of midostaurin as a dual inhibitor of FLT3 and SYK and potentiation of FLT3 inhibition against FLT3-ITD-driven leukemia harboring activated SYK kinase. Oncotarget. 2017;8(32):52026-52044doi: 10.18632/oncotarget.19036.
Weisberg, E. L., Puissant, A., Stone, R., Sattler, M., Buhrlage, S. J., Yang, J., Manley, P. W., Meng, C., Buonopane, M., Daley, J. F., Lazo, S., Wright, R., Weinstock, D. M., Christie, A. L., Stegmaier, K., & Griffin, J. D. (2017). Characterization of midostaurin as a dual inhibitor of FLT3 and SYK and potentiation of FLT3 inhibition against FLT3-ITD-driven leukemia harboring activated SYK kinase. Oncotarget, 8(32), 52026-52044. https://doi.org/10.18632/oncotarget.19036
Weisberg, Ellen L, et al. "Characterization of midostaurin as a dual inhibitor of FLT3 and SYK and potentiation of FLT3 inhibition against FLT3-ITD-driven leukemia harboring activated SYK kinase." Oncotarget vol. 8,32 (2017): 52026-52044. doi: https://doi.org/10.18632/oncotarget.19036
Weisberg EL, Puissant A, Stone R, Sattler M, Buhrlage SJ, Yang J, Manley PW, Meng C, Buonopane M, Daley JF, Lazo S, Wright R, Weinstock DM, Christie AL, Stegmaier K, Griffin JD. Characterization of midostaurin as a dual inhibitor of FLT3 and SYK and potentiation of FLT3 inhibition against FLT3-ITD-driven leukemia harboring activated SYK kinase. Oncotarget. 2017 Jul 06;8(32):52026-52044. doi: 10.18632/oncotarget.19036. eCollection 2017 Aug 08. PMID: 28881711; PMCID: PMC5581010.
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Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation.

International journal of molecular sciences

Navarro S, Stegner D, Nieswandt B, Heemskerk JWM, Kuijpers MJE.
PMID: 35008781
Int J Mol Sci. 2021 Dec 29;23(1). doi: 10.3390/ijms23010358.

In hemostasis and thrombosis, the complex process of thrombus formation involves different molecular pathways of platelet and coagulation activation. These pathways are considered as operating together at the same time, but this has not been investigated. The objective of...

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Navarro S, Stegner D, Nieswandt B, et al. Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation. Int J Mol Sci. 2021;23(1)doi: 10.3390/ijms23010358.
Navarro, S., Stegner, D., Nieswandt, B., Heemskerk, J. W. M., & Kuijpers, M. J. E. (2021). Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation. International journal of molecular sciences, 23(1), . https://doi.org/10.3390/ijms23010358
Navarro, Stefano, et al. "Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation." International journal of molecular sciences vol. 23,1 (2021). doi: https://doi.org/10.3390/ijms23010358
Navarro S, Stegner D, Nieswandt B, Heemskerk JWM, Kuijpers MJE. Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation. Int J Mol Sci. 2021 Dec 29;23(1). doi: 10.3390/ijms23010358. PMID: 35008781.
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Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation.

Journal of personalized medicine

Biswas P, Dey D, Rahman A, Islam MA, Susmi TF, Kaium MA, Hasan MN, Rahman MDH, Mahmud S, Saleh MA, Paul P, Rahman MR, Al Saber M, Song H, Rahman MA, Kim B.
PMID: 34575665
J Pers Med. 2021 Sep 06;11(9). doi: 10.3390/jpm11090888.

BACKGROUND: SYK gene regulates the expression of SYK kinase (Spleen tyrosine kinase), an important non-receptor protein-tyrosine kinase for immunological receptor-mediated signaling, which is also considered a tumor growth metastasis initiator. An onco-informatics analysis was adopted to evaluate the expression...

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Biswas P, Dey D, Rahman A, et al. Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation. J Pers Med. 2021;11(9)doi: 10.3390/jpm11090888.
Biswas, P., Dey, D., Rahman, A., Islam, M. A., Susmi, T. F., Kaium, M. A., Hasan, M. N., Rahman, M. D. H., Mahmud, S., Saleh, M. A., Paul, P., Rahman, M. R., Al Saber, M., Song, H., Rahman, M. A., & Kim, B. (2021). Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation. Journal of personalized medicine, 11(9), . https://doi.org/10.3390/jpm11090888
Biswas, Partha, et al. "Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation." Journal of personalized medicine vol. 11,9 (2021). doi: https://doi.org/10.3390/jpm11090888
Biswas P, Dey D, Rahman A, Islam MA, Susmi TF, Kaium MA, Hasan MN, Rahman MDH, Mahmud S, Saleh MA, Paul P, Rahman MR, Al Saber M, Song H, Rahman MA, Kim B. Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation. J Pers Med. 2021 Sep 06;11(9). doi: 10.3390/jpm11090888. PMID: 34575665; PMCID: PMC8470848.
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BAFF signaling in health and disease.

Current opinion in immunology

Schweighoffer E, Tybulewicz VL.
PMID: 34352467
Curr Opin Immunol. 2021 Aug;71:124-131. doi: 10.1016/j.coi.2021.06.014. Epub 2021 Aug 02.

BAFF is a critical cytokine supporting the survival of mature naïve B cells, acting through the BAFFR receptor. Recent studies show that BAFF and BAFFR are also required for the survival of memory B cells, autoimmune B cells as...

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Schweighoffer E, Tybulewicz VL. BAFF signaling in health and disease. Curr Opin Immunol. 2021;71:124-131doi: 10.1016/j.coi.2021.06.014.
Schweighoffer, E., & Tybulewicz, V. L. (2021). BAFF signaling in health and disease. Current opinion in immunology, 71124-131. https://doi.org/10.1016/j.coi.2021.06.014
Schweighoffer, Edina, and Tybulewicz, Victor Lj. "BAFF signaling in health and disease." Current opinion in immunology vol. 71 (2021): 124-131. doi: https://doi.org/10.1016/j.coi.2021.06.014
Schweighoffer E, Tybulewicz VL. BAFF signaling in health and disease. Curr Opin Immunol. 2021 Aug;71:124-131. doi: 10.1016/j.coi.2021.06.014. Epub 2021 Aug 02. PMID: 34352467.
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Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of .

Frontiers in immunology

Wu SY, Huang JH, Chen WY, Chan YC, Lin CH, Chen YC, Liu FT, Wu-Hsieh BA.
PMID: 28217127
Front Immunol. 2017 Feb 03;8:48. doi: 10.3389/fimmu.2017.00048. eCollection 2017.

Invasive candidiasis is a leading cause of nosocomial bloodstream infection. Neutrophils are the important effector cells in host resistance to candidiasis. To investigate the modulation of neutrophil fungicidal function will advance our knowledge on the control of candidiasis. While...

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Wu SY, Huang JH, Chen WY, et al. Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of . Front Immunol. 2017;8:48doi: 10.3389/fimmu.2017.00048.
Wu, S. Y., Huang, J. H., Chen, W. Y., Chan, Y. C., Lin, C. H., Chen, Y. C., Liu, F. T., & Wu-Hsieh, B. A. (2017). Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of . Frontiers in immunology, 848. https://doi.org/10.3389/fimmu.2017.00048
Wu, Sheng-Yang, et al. "Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of ." Frontiers in immunology vol. 8 (2017): 48. doi: https://doi.org/10.3389/fimmu.2017.00048
Wu SY, Huang JH, Chen WY, Chan YC, Lin CH, Chen YC, Liu FT, Wu-Hsieh BA. Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of . Front Immunol. 2017 Feb 03;8:48. doi: 10.3389/fimmu.2017.00048. eCollection 2017. PMID: 28217127; PMCID: PMC5289966.
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Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21.

Frontiers in immunology

Welsby I, Detienne S, N'Kuli F, Thomas S, Wouters S, Bechtold V, De Wit D, Gineste R, Reinheckel T, Elouahabi A, Courtoy PJ, Didierlaurent AM, Goriely S.
PMID: 28105029
Front Immunol. 2017 Jan 05;7:663. doi: 10.3389/fimmu.2016.00663. eCollection 2016.

The adjuvant properties of the saponin QS-21 have been known for decades. It is a component of the Adjuvant System AS01 that is used in several vaccine candidates. QS-21 strongly potentiates both cellular and humoral immune responses to purified...

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Welsby I, Detienne S, N'Kuli F, et al. Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21. Front Immunol. 2017;7:663doi: 10.3389/fimmu.2016.00663.
Welsby, I., Detienne, S., N'Kuli, F., Thomas, S., Wouters, S., Bechtold, V., De Wit, D., Gineste, R., Reinheckel, T., Elouahabi, A., Courtoy, P. J., Didierlaurent, A. M., & Goriely, S. (2016). Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21. Frontiers in immunology, 7663. https://doi.org/10.3389/fimmu.2016.00663
Welsby, Iain, et al. "Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21." Frontiers in immunology vol. 7 (2016): 663. doi: https://doi.org/10.3389/fimmu.2016.00663
Welsby I, Detienne S, N'Kuli F, Thomas S, Wouters S, Bechtold V, De Wit D, Gineste R, Reinheckel T, Elouahabi A, Courtoy PJ, Didierlaurent AM, Goriely S. Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21. Front Immunol. 2017 Jan 05;7:663. doi: 10.3389/fimmu.2016.00663. eCollection 2016. PMID: 28105029; PMCID: PMC5215313.
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Toxoplasma gondii inhibits mast cell degranulation by suppressing phospholipase Cγ-mediated Ca(2+) mobilization.

Frontiers in microbiology

Smith NL, Abi Abdallah DS, Butcher BA, Denkers EY, Baird B, Holowka D.
PMID: 23847603
Front Microbiol. 2013 Jul 04;4:179. doi: 10.3389/fmicb.2013.00179. eCollection 2013.

Toxoplasma gondii is well-known to subvert normal immune responses, however, mechanisms are incompletely understood. In particular, its capacity to alter receptor-activated Ca(2+)-mediated signaling processes has not been well-characterized. In initial experiments, we found evidence that T. gondii infection inhibits...

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Smith NL, Abi Abdallah DS, Butcher BA, et al. Toxoplasma gondii inhibits mast cell degranulation by suppressing phospholipase Cγ-mediated Ca(2+) mobilization. Front Microbiol. 2013;4:179doi: 10.3389/fmicb.2013.00179.
Smith, N. L., Abi Abdallah, D. S., Butcher, B. A., Denkers, E. Y., Baird, B., & Holowka, D. (2013). Toxoplasma gondii inhibits mast cell degranulation by suppressing phospholipase Cγ-mediated Ca(2+) mobilization. Frontiers in microbiology, 4179. https://doi.org/10.3389/fmicb.2013.00179
Smith, Norah L, et al. "Toxoplasma gondii inhibits mast cell degranulation by suppressing phospholipase Cγ-mediated Ca(2+) mobilization." Frontiers in microbiology vol. 4 (2013): 179. doi: https://doi.org/10.3389/fmicb.2013.00179
Smith NL, Abi Abdallah DS, Butcher BA, Denkers EY, Baird B, Holowka D. Toxoplasma gondii inhibits mast cell degranulation by suppressing phospholipase Cγ-mediated Ca(2+) mobilization. Front Microbiol. 2013 Jul 04;4:179. doi: 10.3389/fmicb.2013.00179. eCollection 2013. PMID: 23847603; PMCID: PMC3701878.
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Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus.

Frontiers in immunology

Rother N, van der Vlag J.
PMID: 26648939
Front Immunol. 2015 Nov 30;6:610. doi: 10.3389/fimmu.2015.00610. eCollection 2015.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against nuclear components. Circulating immune complexes of chromatin and autoantibodies deposit in various tissues leading to inflammation and tissue damage. It has been well documented...

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Rother N, van der Vlag J. Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Front Immunol. 2015;6:610doi: 10.3389/fimmu.2015.00610.
Rother, N., & van der Vlag, J. (2015). Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Frontiers in immunology, 6610. https://doi.org/10.3389/fimmu.2015.00610
Rother, Nils, and van der Vlag, Johan. "Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus." Frontiers in immunology vol. 6 (2015): 610. doi: https://doi.org/10.3389/fimmu.2015.00610
Rother N, van der Vlag J. Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Front Immunol. 2015 Nov 30;6:610. doi: 10.3389/fimmu.2015.00610. eCollection 2015. PMID: 26648939; PMCID: PMC4663269.
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Expression of dectin-1 and enhanced activation of NALP3 inflammasome are associated with resistance to paracoccidioidomycosis.

Frontiers in microbiology

Feriotti C, Bazan SB, Loures FV, Araújo EF, Costa TA, Calich VL.
PMID: 26388856
Front Microbiol. 2015 Sep 03;6:913. doi: 10.3389/fmicb.2015.00913. eCollection 2015.

Dectin-1 is a pattern recognition receptor (PRR) that recognizes β-glucans and plays a major role in the immunity against fungal pathogens. Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis, has a sugar-rich cell wall mainly composed of mannans and glucans....

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Feriotti C, Bazan SB, Loures FV, et al. Expression of dectin-1 and enhanced activation of NALP3 inflammasome are associated with resistance to paracoccidioidomycosis. Front Microbiol. 2015;6:913doi: 10.3389/fmicb.2015.00913.
Feriotti, C., Bazan, S. B., Loures, F. V., Araújo, E. F., Costa, T. A., & Calich, V. L. (2015). Expression of dectin-1 and enhanced activation of NALP3 inflammasome are associated with resistance to paracoccidioidomycosis. Frontiers in microbiology, 6913. https://doi.org/10.3389/fmicb.2015.00913
Feriotti, Claudia, et al. "Expression of dectin-1 and enhanced activation of NALP3 inflammasome are associated with resistance to paracoccidioidomycosis." Frontiers in microbiology vol. 6 (2015): 913. doi: https://doi.org/10.3389/fmicb.2015.00913
Feriotti C, Bazan SB, Loures FV, Araújo EF, Costa TA, Calich VL. Expression of dectin-1 and enhanced activation of NALP3 inflammasome are associated with resistance to paracoccidioidomycosis. Front Microbiol. 2015 Sep 03;6:913. doi: 10.3389/fmicb.2015.00913. eCollection 2015. PMID: 26388856; PMCID: PMC4558525.
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Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study.

Experimental dermatology

Walker A, Erwig L, Foster K, Nevin K, Wenzel J, Worm M, Williams N, Ratia N, Hoang B, Schneider-Merck T, Gisbert S, Carnarius H, Dickson M.
PMID: 33336508
Exp Dermatol. 2021 Nov;30(11):1686-1692. doi: 10.1111/exd.14253. Epub 2020 Dec 17.

The immunoregulator spleen tyrosine kinase (SYK) is upregulated in cutaneous lupus erythematosus (CLE). This double-blind, multicentre, Phase Ib study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of the selective SYK inhibitor GSK2646264 in active CLE lesions. Two...

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Walker A, Erwig L, Foster K, et al. Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. Exp Dermatol. 2020;30(11):1686-1692doi: 10.1111/exd.14253.
Walker, A., Erwig, L., Foster, K., Nevin, K., Wenzel, J., Worm, M., Williams, N., Ratia, N., Hoang, B., Schneider-Merck, T., Gisbert, S., Carnarius, H., & Dickson, M. (2021). Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. Experimental dermatology, 30(11), 1686-1692. https://doi.org/10.1111/exd.14253
Walker, Alex, et al. "Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study." Experimental dermatology vol. 30,11 (2021): 1686-1692. doi: https://doi.org/10.1111/exd.14253
Walker A, Erwig L, Foster K, Nevin K, Wenzel J, Worm M, Williams N, Ratia N, Hoang B, Schneider-Merck T, Gisbert S, Carnarius H, Dickson M. Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. Exp Dermatol. 2021 Nov;30(11):1686-1692. doi: 10.1111/exd.14253. Epub 2020 Dec 17. PMID: 33336508; PMCID: PMC8596667.
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Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis.

Scientific reports

Novikov FN, Panova MV, Titov IY, Stroylov VS, Stroganov OV, Chilov GG.
PMID: 34848799
Sci Rep. 2021 Nov 30;11(1):23120. doi: 10.1038/s41598-021-02568-6.

The pathophysiology of osteoarthritis (OA) includes the destruction of subchondral bone tissue and inflammation of the synovium. Thus, an effective disease-modifying treatment should act on both of these pathogenetic components. It is known that cSrc kinase is involved in...

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Novikov FN, Panova MV, Titov IY, et al. Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis. Sci Rep. 2021;11(1):23120doi: 10.1038/s41598-021-02568-6.
Novikov, F. N., Panova, M. V., Titov, I. Y., Stroylov, V. S., Stroganov, O. V., & Chilov, G. G. (2021). Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis. Scientific reports, 11(1), 23120. https://doi.org/10.1038/s41598-021-02568-6
Novikov, F N, et al. "Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis." Scientific reports vol. 11,1 (2021): 23120. doi: https://doi.org/10.1038/s41598-021-02568-6
Novikov FN, Panova MV, Titov IY, Stroylov VS, Stroganov OV, Chilov GG. Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis. Sci Rep. 2021 Nov 30;11(1):23120. doi: 10.1038/s41598-021-02568-6. PMID: 34848799; PMCID: PMC8632988.
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Impact of Interindividual Differences in Plasma Fraction Unbound on the Pharmacokinetics of a Novel Syk Kinase Inhibitor in Beagle Dogs.

Drug metabolism and disposition: the biological fate of chemicals

Pike A, Jones B, Markandu R, O'Neill D, Putra IP.
PMID: 34135088
Drug Metab Dispos. 2021 Sep;49(9):736-742. doi: 10.1124/dmd.121.000409. Epub 2021 Jun 16.

Inconsistencies in pharmacokinetic parameters between individual animals in preclinical studies are a common occurrence. Often such differences between animals are simply accepted as experimental variability rather than as indications of specific differences in animal phenotype that could lead to...

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Pike A, Jones B, Markandu R, et al. Impact of Interindividual Differences in Plasma Fraction Unbound on the Pharmacokinetics of a Novel Syk Kinase Inhibitor in Beagle Dogs. Drug Metab Dispos. 2021;49(9):736-742doi: 10.1124/dmd.121.000409.
Pike, A., Jones, B., Markandu, R., O'Neill, D., & Putra, I. P. (2021). Impact of Interindividual Differences in Plasma Fraction Unbound on the Pharmacokinetics of a Novel Syk Kinase Inhibitor in Beagle Dogs. Drug metabolism and disposition: the biological fate of chemicals, 49(9), 736-742. https://doi.org/10.1124/dmd.121.000409
Pike, Andy, et al. "Impact of Interindividual Differences in Plasma Fraction Unbound on the Pharmacokinetics of a Novel Syk Kinase Inhibitor in Beagle Dogs." Drug metabolism and disposition: the biological fate of chemicals vol. 49,9 (2021): 736-742. doi: https://doi.org/10.1124/dmd.121.000409
Pike A, Jones B, Markandu R, O'Neill D, Putra IP. Impact of Interindividual Differences in Plasma Fraction Unbound on the Pharmacokinetics of a Novel Syk Kinase Inhibitor in Beagle Dogs. Drug Metab Dispos. 2021 Sep;49(9):736-742. doi: 10.1124/dmd.121.000409. Epub 2021 Jun 16. PMID: 34135088.
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