Evidence map›Paper›PMID 27411717›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.

Walter Kostich, Brian D Hamman, Yu-Wen Li, Sreenivasulu Naidu, Kumaran Dandapani, Jianlin Feng, Amy Easton, Clotilde Bourin, Kevin Baker, Jason Allen and 45 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04631471 (Regeneration in Cervical Degenerative Myelopathy - a Multi-centre, Double-blind, Randomised, Placebo Controlled Trial Assessing the Efficacy of Ibudilast as an Adjuvant Treatment to Decompressive Surgery for Degenerative Cervical Myelopathy), which is not on this map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04631471 phase3recruitingnot on this mapstarted 2021, after this paper: background citation

Regeneration in Cervical Degenerative Myelopathy - a Multi-centre, Double-blind, Randomised, Placebo Controlled Trial Assessing the Efficacy of Ibudilast as an Adjuvant Treatment to Decompressive Surgery for Degenerative Cervical Myelopathy

TypeinterventionalSponsorCambridge University Hospitals NHS Foundation TrustRan2021 to 2026Enrolled400ConditionsMyelopathy, Spinal Cord DiseasesArmsIbudilast, Cervical decompressive surgery, Matching placebo
3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.

  1. Pooled it
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  11. Evaluation of the Antihyperalgesic Potential ofCurrent issues in molecular biology · 2025
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  13. Diabetic neuropathy: cutting-edge research and future directions.Signal transduction and targeted therapy · 2025
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  15. Population genetic analysis based on the polymorphisms mediated by transposons in the genomes of pig.DNA research : an international journal for rapid publication of reports on genes and genomes · 2024
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  16. Article
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

55 authors at 5 institutions in 2 countries.

Walter KostichResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Brian D HammanResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Yu-Wen LiResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Sreenivasulu NaiduResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Kumaran DandapaniResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Jianlin FengResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Amy EastonResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Clotilde BourinResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Kevin BakerResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Jason AllenResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Katerina SavelievaResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Justin V LouisResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Manoj DokaniaResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Saravanan ElavazhaganResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Pradeep VattikundalaResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Vivek SharmaResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Manish Lal DasResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Ganesh ShankarResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Anoop KumarResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Vinay K HolenarsipurResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Michael GulianelloResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Ted MolskiResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Jeffrey M BrownResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Martin LewisResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Yanling HuangResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Yifeng LuResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Rick PieschlResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Kevin O'MalleyResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Jonathan LippyResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Amr NouraldeenResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Thomas H LanthornResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Guilan YeResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Alan WilsonResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Anand BalakrishnanResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Rex DentonResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
James E GraceResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Kimberley A LentzResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Kenneth S SantoneResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Yingzhi BiResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Alan MainResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Jon SwaffieldResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Ken CarsonResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Sandhya MandlekarResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Reeba K VikramadithyanResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Susheel J NaraResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Carolyn DzierbaResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Joanne BronsonResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
John E MacorResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Robert ZaczekResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Ryan WestphalResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Laszlo KissResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Linda BristowResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Charles M ConwayResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.).
Brian ZambrowiczResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.) Charlie.Albright@BMS.com brian.zambrowicz@regeneron.com.
Charles F AlbrightResearch and Development, Neuroscience Biology (W.K., Y.-W.L., J.F., A.E., C.B., M.G., T.M., J.M.B., M.L., Y.H., Y.L., R.P., R.Z., R.W., L.K., L.B., C.M.C., C.F.A.), Neuroscience Chemistry (C.D., J.B., J.E.M.), Preclinical Candidate Optimization (A.B., J.E.G., K.A.L., K.S.S.), and Discovery Toxicology (R.D.), Bristol-Myers Squibb, Wallingford, Connecticut; Research and Development, Leads Discovery and Optimization, Bristol-Myers Squibb, Pennington, New Jersey (K.O., J.L.); BMS Biocon Research Center, Bangalore, India (K.D., J.V.L., S.N., M.D., S.E., P.V., V.S., M.L.D, G.S., A.K., V.K.H., S.M., R.K.V., S.J.N.); Lexicon Pharmaceuticals, The Woodlands, Texas (B.D.H., K.B., J.A., K.S., A.N., A.W., J.S., B.Z., T.H.L., G.Y.); and Lexicon Pharmaceuticals, Basking Ridge, New Jersey (Y.B., A.M., K.C.) Charlie.Albright@BMS.com brian.zambrowicz@regeneron.com.
Biocon (India) · INBristol-Myers Squibb (United States) · USCoastal Connecticut Research (United States) · USLexicon Pharmaceuticals (United States) · USMACOM (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor-induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2 adrenergic signaling, a pathway known to be antinociceptive in humans.

Indexed as

AnimalsElectrophysiological PhenomenaGene Knockout TechniquesHEK293 CellsHumansMaleMiceNeuralgiaNociceptionPhenotypeProtein Kinase InhibitorsProtein Serine-Threonine KinasesRatsSpinal CordProtein Kinase InhibitorsProtein Serine-Threonine Kinases

Identifiers

PMID27411717
PMCPMC4998676
OpenAlexW2475203061

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