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The small molecule CLP257 does not modify activity of the K+–Cl co-transporter KCC2 but does potentiate GABAA receptor activity

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Figure 1: CLP257 does not affect KCC2 function.


  1. 1

    Moore, Y.E., Kelley, M.R., Brandon, N.J., Deeb, T.Z. & Moss, S.J. Trends Neurosci. 40, 555–571 (2017).

    CAS  Article  Google Scholar 

  2. 2

    Gagnon, M. et al. Nat. Med. 19, 1524–1528 (2013).

    CAS  Article  Google Scholar 

  3. 3

    Delpire, E. et al. Bioorg. Med. Chem. Lett. 22, 4532–4535 (2012).

    CAS  Article  Google Scholar 

  4. 4

    Rouzaire-Dubois, B., Bostel, S. & Dubois, J.M. Neuroscience 88, 307–317 (1999).

    CAS  Article  Google Scholar 

  5. 5

    Rowe, S.M. & Verkman, A.S. Cold Spring Harb. Perspect. Med. 3, a009761 (2013).

    Article  Google Scholar 

  6. 6

    Williams, J.R., Sharp, J.W., Kumari, V.G., Wilson, M. & Payne, J.A. J. Biol. Chem. 274, 12656–12664 (1999).

    CAS  Article  Google Scholar 

  7. 7

    Zhang, D., Gopalakrishnan, S.M., Freiberg, G. & Surowy, C.S. J. Biomol. Screen. 15, 177–184 (2010).

    CAS  Article  Google Scholar 

  8. 8

    Payne, J.A. Am. J. Physiol. 273, C1516–C1525 (1997).

    CAS  Article  Google Scholar 

  9. 9

    Delpire, E. et al. Proc. Natl. Acad. Sci. USA 106, 5383–5388 (2009).

    CAS  Article  Google Scholar 

  10. 10

    Friedel, P. et al. Sci. Signal. 8, ra65 (2015).

    Article  Google Scholar 

  11. 11

    Bornhop, D.J. et al. Science 317, 1732–1736 (2007).

    CAS  Article  Google Scholar 

  12. 12

    Hamidi, S. & Avoli, M. Neurobiol. Dis. 79, 51–58 (2015).

    CAS  Article  Google Scholar 

  13. 13

    Ostroumov, A. et al. Neuron 92, 493–504 (2016).

    CAS  Article  Google Scholar 

  14. 14

    Ferando, I., Faas, G.C. & Mody, I. Nat. Neurosci. 19, 1197–1200 (2016).

    CAS  Article  Google Scholar 

  15. 15

    Ferrini, F., Lorenzo, L.E., Godin, A.G., Quang, M.L. & De Koninck, Y. Sci. Rep. 7, 3870 (2017).

    Article  Google Scholar 

  16. 16

    Friedel, P., Bregestovski, P. & Medina, I. Front. Mol. Neurosci. 6, 7 (2013).

    CAS  Article  Google Scholar 

  17. 17

    Deeb, T.Z., Nakamura, Y., Frost, G.D., Davies, P.A. & Moss, S.J. Eur. J. Neurosci. 38, 2453–2467 (2013).

    Article  Google Scholar 

  18. 18

    Pellegrino, C. et al. J. Physiol. (Lond.) 589, 2475–2496 (2011).

    CAS  Article  Google Scholar 

  19. 19

    Sivakumaran, S. et al. J. Neurosci. 35, 8291–8296 (2015).

    CAS  Article  Google Scholar 

  20. 20

    Grimley, J.S. et al. J. Neurosci. 33, 16297–16309 (2013).

    CAS  Article  Google Scholar 

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We would like to thank S. Geschwindner for critical comments and discussion on the manuscript. We would like to thank G.J. Augustine (Korea Institute of Science and Technology) for generously providing the SuperClomeleon construct. This work was supported by funding from AstraZeneca, a grant from the Simons Foundation (206026 to S.J.M.), NIH–NINDS grants NS051195, NS056359, NS081735, and NS087662 (S.J.M.), and NIH–NIMH MH097446 (P.A.D.).

Author information




R.A.C., T.Z.D., I.M., P.A.D., S.Z., J.D., R.J.M., N.J.B., and S.J.M. designed experiments. R.A.C., K.J., L.I.P., H.J.W., L.J.M., D.J.B., I.C., J.G., L.S., and T.Z.D. performed all the experiments and subsequent analysis. P.M.S., M.P.B., D.H.M., N.D., J.H., M.E.D., R.J.M., and Q.W. produced all reagents or oversaw production of reagents. R.A.C., T.Z.D., I.M., N.J.B., and S.J.M. wrote the manuscript.

Corresponding authors

Correspondence to Nicholas J Brandon or Tarek Z Deeb or Stephen J Moss.

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Competing interests

K.J., L.J.M., P.M.S., M.P.B., D.J.B., N.D., R.J.M., S.Z., Q.W., J.H., M.E.D., J.D., and N.J.B. are or were full-time employees and shareholders of AstraZeneca. S.J.M. serves as a consultant for SAGE therapeutics and AstraZeneca; these relationships are regulated by Tufts University.

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Cardarelli, R., Jones, K., Pisella, L. et al. The small molecule CLP257 does not modify activity of the K+–Cl co-transporter KCC2 but does potentiate GABAA receptor activity. Nat Med 23, 1394–1396 (2017).

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