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Research ArticleDrug Discovery and Translational Medicine

Dual Inhibition of Bruton’s Tyrosine Kinase and Phosphoinositide-3-Kinase p110δ as a Therapeutic Approach to Treat Non-Hodgkin’s B Cell Malignancies

Jennifer Alfaro, Felipe Pérez de Arce, Sebastián Belmar, Glenda Fuentealba, Patricio Avila, Gonzalo Ureta, Camila Flores, Claudia Acuña, Luz Delgado, Diana Gaete, Brahmam Pujala, Anup Barde, Anjan K. Nayak, T. V. R. Upendra, Dhananjay Patel, Shailender Chauhan, Vijay K. Sharma, Stacy Kanno, Ramona G. Almirez, David T. Hung, Sarvajit Chakravarty, Roopa Rai, Sebastián Bernales, Kevin P. Quinn, Son M. Pham and Emma McCullagh
Journal of Pharmacology and Experimental Therapeutics May 2017, 361 (2) 312-321; DOI: https://doi.org/10.1124/jpet.116.238022
Jennifer Alfaro
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Felipe Pérez de Arce
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Sebastián Belmar
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Glenda Fuentealba
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Patricio Avila
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Gonzalo Ureta
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Camila Flores
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Claudia Acuña
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Luz Delgado
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Diana Gaete
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Brahmam Pujala
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Anup Barde
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Anjan K. Nayak
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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T. V. R. Upendra
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Dhananjay Patel
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Shailender Chauhan
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Vijay K. Sharma
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Stacy Kanno
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Ramona G. Almirez
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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David T. Hung
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Sarvajit Chakravarty
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Roopa Rai
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Sebastián Bernales
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Kevin P. Quinn
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Son M. Pham
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Emma McCullagh
Translational Research Group, Fundación Ciencia y Vida, Santiago, Chile (J.A., F.P.d.A., S.Bel., G.F., P.A., G.U., C.F., C.A., L.D., D.G.); Biological Sciences Department, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Región de Valparaíso, Chile (F.P.d.A., S.Bel.); Chemistry Group, Integral BioSciences, Pvt. Ltd., Noida, India (B.P., A.B., A.K.N., T.V.R.U., D.P., S.C., V.K.S.); and Discovery Research, Medivation, Inc., now Pfizer, San Francisco, California (S.K., R.G.A., D.T.H., S.C., R.R., S.Ber., K.P.Q., S.M.P., E.M.)
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Journal of Pharmacology and Experimental Therapeutics: 361 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 361, Issue 2
1 May 2017
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Dual Inhibition of BTK and PI3Kδ to Treat B Cell Cancers

Jennifer Alfaro, Felipe Pérez de Arce, Sebastián Belmar, Glenda Fuentealba, Patricio Avila, Gonzalo Ureta, Camila Flores, Claudia Acuña, Luz Delgado, Diana Gaete, Brahmam Pujala, Anup Barde, Anjan K. Nayak, T. V. R. Upendra, Dhananjay Patel, Shailender Chauhan, Vijay K. Sharma, Stacy Kanno, Ramona G. Almirez, David T. Hung, Sarvajit Chakravarty, Roopa Rai, Sebastián Bernales, Kevin P. Quinn, Son M. Pham and Emma McCullagh
Journal of Pharmacology and Experimental Therapeutics May 1, 2017, 361 (2) 312-321; DOI: https://doi.org/10.1124/jpet.116.238022

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Research ArticleDrug Discovery and Translational Medicine

Dual Inhibition of BTK and PI3Kδ to Treat B Cell Cancers

Jennifer Alfaro, Felipe Pérez de Arce, Sebastián Belmar, Glenda Fuentealba, Patricio Avila, Gonzalo Ureta, Camila Flores, Claudia Acuña, Luz Delgado, Diana Gaete, Brahmam Pujala, Anup Barde, Anjan K. Nayak, T. V. R. Upendra, Dhananjay Patel, Shailender Chauhan, Vijay K. Sharma, Stacy Kanno, Ramona G. Almirez, David T. Hung, Sarvajit Chakravarty, Roopa Rai, Sebastián Bernales, Kevin P. Quinn, Son M. Pham and Emma McCullagh
Journal of Pharmacology and Experimental Therapeutics May 1, 2017, 361 (2) 312-321; DOI: https://doi.org/10.1124/jpet.116.238022
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