Next Article in Journal
Effects of Early Life Stress on Bone Homeostasis in Mice and Humans
Next Article in Special Issue
Functional and Pharmacological Comparison of Human, Mouse, and Rat Organic Cation Transporter 1 toward Drug and Pesticide Interaction
Previous Article in Journal
Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies
Previous Article in Special Issue
The Impact of Genetic Polymorphisms in Organic Cation Transporters on Renal Drug Disposition
Article

Tofacitinib and Baricitinib Are Taken up by Different Uptake Mechanisms Determining the Efficacy of Both Drugs in RA

1
Experimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany
2
Department of Orthopedic Surgery, Otto-von-Guericke University, 39120 Magdeburg, Germany
3
Institute of Inorganic and Analytical Chemistry, University of Münster, 48149 Münster, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6632; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186632
Received: 27 August 2020 / Revised: 3 September 2020 / Accepted: 9 September 2020 / Published: 10 September 2020
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease in which synovial fibroblasts (SF) play a key role. Baricitinib and Tofacitinib both act intracellularly, blocking the ATP-binding side of JAK proteins and thereby the downstream signalling pathway via STAT-3. Therefore, we investigated the role of organic cation transporters (OCTs) in Baricitinib and Tofacitinib cellular transport. Methods: OCT expression was analysed in SF isolated from RA and osteoarthritis (OA) patients, as well as peripheral blood mononuclear cells. The interaction of Baricitinib and Tofacitinib with OCTs was investigated using quenching experiments. The intracellular accumulation of both drugs was quantified using LC/MS. Target inhibition for both drugs was tested using Western blot for phosphorylated JAK1 and STAT3 upon stimulation with IL-6. Results: MATE-1 expression increased in OASF compared to RASF. The other OCTs were not differentially expressed. The transport of Baricitinib was not OCT dependent. Tofacitinib; however, was exported from RASF in a MATE-1 dependent way. Tofacitinib and Baricitinib showed comparable inhibition of downstream signalling pathways. Conclusion: We observed different cellular uptake strategies for Baricitinib and Tofacitinib. Tofacitinib was exported out of healthy cells due to the increased expression of MATE1. This might make Tofacitinib the favourable drug. View Full-Text
Keywords: RA; Tofacitinib; Baricitinib; organic cation transporter; MATE1 RA; Tofacitinib; Baricitinib; organic cation transporter; MATE1
Show Figures

Figure 1

MDPI and ACS Style

Amrhein, J.; Drynda, S.; Schlatt, L.; Karst, U.; Lohmann, C.H.; Ciarimboli, G.; Bertrand, J. Tofacitinib and Baricitinib Are Taken up by Different Uptake Mechanisms Determining the Efficacy of Both Drugs in RA. Int. J. Mol. Sci. 2020, 21, 6632. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186632

AMA Style

Amrhein J, Drynda S, Schlatt L, Karst U, Lohmann CH, Ciarimboli G, Bertrand J. Tofacitinib and Baricitinib Are Taken up by Different Uptake Mechanisms Determining the Efficacy of Both Drugs in RA. International Journal of Molecular Sciences. 2020; 21(18):6632. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186632

Chicago/Turabian Style

Amrhein, Jan, Susanne Drynda, Lukas Schlatt, Uwe Karst, Christoph H. Lohmann, Giuliano Ciarimboli, and Jessica Bertrand. 2020. "Tofacitinib and Baricitinib Are Taken up by Different Uptake Mechanisms Determining the Efficacy of Both Drugs in RA" International Journal of Molecular Sciences 21, no. 18: 6632. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186632

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop