Discovery of novel brain permeable and G protein-biased beta-1 adrenergic receptor partial agonists for the treatment of neurocognitive disorders

PLoS ONE

Volumn 12, Issue 7, 2017, Pages

  Yi, Bitna ^a   Jahangir, Alam ^a   Evans, Andrew K ^a   Briggs, Denise ^a   Ravina, Kristine ^a   Ernest, Jacqueline ^a   Farimani, Amir B ^b   Sun, Wenchao ^a   Rajadas, Jayakumar ^a   Green, Michael ^a   Feinberg, Evan N ^b   Pande, Vijay S ^b   Shamloo, Mehrdad ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 HYDROXY 3 [2 (2 METHOXYPHENOXY)ETHYLAMINO]PROPOXY]PHENOL; BETA 1 ADRENERGIC RECEPTOR STIMULATING AGENT; BETA ARRESTIN; GUANINE NUCLEOTIDE BINDING PROTEIN; ISOPRENALINE; LIPOPOLYSACCHARIDE; PROPRANOLOL; STD 101 D1; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; VERAPAMIL; XAMOTEROL; ADRB1 PROTEIN, HUMAN; BETA 1 ADRENERGIC RECEPTOR; DIPHENYL ETHER DERIVATIVE; PROPANOLAMINE DERIVATIVE; PROTEIN BINDING; STD-101-D1;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISORDERS OF HIGHER CEREBRAL FUNCTION; DRUG ABSORPTION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG SYNTHESIS; EC50; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NEWBORN; NONHUMAN; RAT; SIGNAL TRANSDUCTION; ANIMAL; BRAIN; C57BL MOUSE; CELL CULTURE; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; CHO CELL LINE; CRICETULUS; DRUG DEVELOPMENT; HAMSTER; HUMAN; METABOLISM; MOLECULAR MODEL; NEUROCOGNITIVE DISORDERS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PERMEABILITY; SPRAGUE DAWLEY RAT; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE; X RAY CRYSTALLOGRAPHY;

ADRENERGIC BETA-1 RECEPTOR AGONISTS; ALZHEIMER DISEASE; ANIMALS; BRAIN; CELL LINE, TUMOR; CELLS, CULTURED; CHO CELLS; CRICETINAE; CRICETULUS; CRYSTALLOGRAPHY, X-RAY; DRUG DISCOVERY; GTP-BINDING PROTEINS; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICE, INBRED C57BL; MODELS, CHEMICAL; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NEUROCOGNITIVE DISORDERS; PERMEABILITY; PHENYL ETHERS; PROPANOLAMINES; PROTEIN BINDING; RATS, SPRAGUE-DAWLEY; RECEPTORS, ADRENERGIC, BETA-1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 85026211104     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0180319     Document Type: Article

References (64)

1. Hall RA. Beta-adrenergic receptors and their interacting proteins. Semin Cell Dev Biol. 2004; 15 (3):281–8. https://doi.org/10.1016/j.semcdb.2003.12.017 PMID: 15125891.
2. Bylund DB, Eikenberg DC, Hieble JP, Langer SZ, Lefkowitz RJ, Minneman KP, et al. International Union of Pharmacology nomenclature of adrenoceptors. Pharmacol Rev. 1994; 46(2):121–36. PMID: 7938162.
3. Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009; 10 (3):211–23. Epub 2009/02/05. nrn2573 10.1038/nrn2573. PMID: 19190638. https://doi.org/10.1038/nrn2573
4. Feinstein DL, Heneka MT, Gavrilyuk V, Dello Russo C, Weinberg G, Galea E. Noradrenergic regulation of inflammatory gene expression in brain. Neurochem Int. 2002; 41(5):357–65. Epub 2002/08/15. S0197018602000499. PMID: 12176079.
5. Gorman AL, Dunn AJ. Beta-adrenergic receptors are involved in stress-related behavioral changes. Pharmacol Biochem Behav. 1993; 45(1):1–7. PMID: 8100069.
6. Philipp M, Hein L. Adrenergic receptor knockout mice: distinct functions of 9 receptor subtypes. Pharmacol Ther. 2004; 101(1):65–74. PMID: 14729393.
7. Frishman WH. beta-Adrenergic blockade in cardiovascular disease. J Cardiovasc Pharmacol Ther. 2013; 18(4):310–9. https://doi.org/10.1177/1074248413484986 PMID: 23637119.
8. Cruickshank JM. Beta-blockers and heart failure. Indian Heart J. 62(2):101–10. Epub 2010/12/25. PMID: 21180298.
9. Coutellier L, Ardestani PM, Shamloo M. beta1-adrenergic receptor activation enhances memory in Alzheimer’s disease model. Ann Clin Transl Neurol. 2014; 1(5):348–60. Epub 2014/06/03. https://doi.org/10.1002/acn3.57 PMID: 24883337; PubMed Central PMCID: PMC4036739.
10. Faizi M, Bader PL, Tun C, Encarnacion A, Kleschevnikov A, Belichenko P, et al. Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down syndrome: activation of beta1-adrenergic receptor by xamoterol as a potential cognitive enhancer. Neurobiol Dis. 2011; 43(2):397–413. Epub 2011/04/30. https://doi.org/10.1016/j.nbd.2011.04.011 PMID: 21527343; PubMed Central PMCID: PMC3539757.
11. Ardestani PM, Evans AK, Yi B, Nguyen T, Coutellier L, Shamloo M. Modulation of neuroinflammation and pathology in the 5XFAD mouse model of Alzheimer’s disease using a biased and selective beta-1 adrenergic receptor partial agonist. Neuropharmacology. 2017; 116:371–86. https://doi.org/10.1016/j.neuropharm.2017.01.010 PMID: 28089846; PubMed Central PMCID: PMCPMC5385159.
12. Madrigal JL, Feinstein DL, Dello Russo C. Norepinephrine protects cortical neurons against microglial-induced cell death. J Neurosci Res. 2005; 81(3):390–6. https://doi.org/10.1002/jnr.20481 PMID: 15948176.
13. Madrigal JL, Leza JC, Polak P, Kalinin S, Feinstein DL. Astrocyte-derived MCP-1 mediates neuroprotective effects of noradrenaline. J Neurosci. 2009; 29(1):263–7. Epub 2009/01/09. https://doi.org/10.1523/JNEUROSCI.4926-08.2009 PMID: 19129402.
14. Markus T, Hansson SR, Cronberg T, Cilio C, Wieloch T, Ley D. beta-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices. J Neuroinflammation. 2010; 7:94. https://doi.org/10.1186/1742-2094-7-94 PMID: 21172031; PubMed Central PMCID: PMCPMC3017519.
15. Violin JD, Lefkowitz RJ. Beta-arrestin-biased ligands at seven-transmembrane receptors. Trends Pharmacol Sci. 2007; 28(8):416–22. https://doi.org/10.1016/j.tips.2007.06.006 PMID: 17644195.
16. van der Westhuizen ET, Breton B, Christopoulos A, Bouvier M. Quantification of ligand bias for clinically relevant beta2-adrenergic receptor ligands: implications for drug taxonomy. Mol Pharmacol. 2014; 85 (3):492–509. https://doi.org/10.1124/mol.113.088880 PMID: 24366668.
17. Kenakin T, Christopoulos A. Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat Rev Drug Discov. 2013; 12(3):205–16. https://doi.org/10.1038/nrd3954 PMID: 23411724.
18. Bastain W, Boyce MJ, Stafford LE, Morton PB, Clarke DA, Marlow HF. Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers. Eur J Clin Pharmacol. 1988; 34(5):469–73. Epub 1988/01/01. PMID: 2904884.
19. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3(6):1101–8. PMID: 18546601.
20. Strubbe JH, Bruggink JE, Steffens AB. Hepatic portal vein cannulation for infusion and blood sampling in freely moving rats. Physiol Behav. 1999; 65(4–5):885–7. PMID: 10073496.
21. Murakami T, Nakanishi M, Yoshimori T, Okamura N, Norikura R, Mizojiri K. Separate assessment of intestinal and hepatic first-pass effects using a rat model with double cannulation of the portal and jugular veins. Drug Metab Pharmacokinet. 2003; 18(4):252–60. PMID: 15618743.
22. Kusiak JW, Heja G, Pitha J. Two beta-adrenergic pharmacophores on the same molecule. A set of agonist-antagonist combinations. Biochem Pharmacol. 1987; 36(2):269–75. Epub 1987/01/15. 0006-2952 (87)90700-3. PMID: 2880591.
23. Ma SL, Tang NL, Lam LC, Chiu HF. Association between tumor necrosis factor-alpha promoter polymorphism and Alzheimer’s disease. Neurology. 2004; 62(2):307–9. PMID: 14745077.
24. Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, et al. Elevated circulating tumor necrosis factor levels in Alzheimer’s disease. Neurosci Lett. 1991; 129(2):318–20. PMID: 1745413.
25. McCoy MK, Tansey MG. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflammation. 2008; 5:45. https://doi.org/10.1186/1742-2094-5-45PMID: 18925972; PubMed Central PMCID: PMCPMC2577641.
26. Besnard J, Ruda GF, Setola V, Abecassis K, Rodriguiz RM, Huang XP, et al. Automated design of ligands to polypharmacological profiles. Nature. 2012; 492(7428):215–20. https://doi.org/10.1038/nature11691 PMID: 23235874; PubMed Central PMCID: PMCPMC3653568.
27. Murchison CF, Zhang XY, Zhang WP, Ouyang M, Lee A, Thomas SA. A distinct role for norepinephrine in memory retrieval. Cell. 2004; 117(1):131–43. Epub 2004/04/07. S0092867404002594. PMID: 15066288.
28. Suzuki A, Fukushima H, Mukawa T, Toyoda H, Wu LJ, Zhao MG, et al. Upregulation of CREB-mediated transcription enhances both short- and long-term memory. J Neurosci. 2011; 31(24):8786–802. Epub 2011/06/17. https://doi.org/10.1523/JNEUROSCI.3257-10.2011 PMID: 21677163.
29. De Luca A, Giuditta A. Role of a transcription factor (CREB) in memory processes. Riv Biol. 1997; 90 (3):371–84. Epub 1997/01/01. PMID: 9549403.
30. Waller DG, Webster J, Sykes CA, Bhalla KK, Wray R. Clinical efficacy of xamoterol, a beta 1-adreno-ceptor partial agonist, in mild to moderate heart failure. U.K. Xamoterol Study Group. Eur Heart J. 1989; 10(11):1003–10. Epub 1989/11/01. PMID: 2574108.
31. Ang EL, Chan WL, Cleland JG, Moore D, Krikler SJ, Alexander ND, et al. Placebo controlled trial of xamoterol versus digoxin in chronic atrial fibrillation. Br Heart J. 1990; 64(4):256–60. PMID: 1977430; PubMed Central PMCID: PMCPMC1024416.
32. Kenakin T. Functional selectivity and biased receptor signaling. J Pharmacol Exp Ther. 2011; 336 (2):296–302. https://doi.org/10.1124/jpet.110.173948 PMID: 21030484.
33. Rajagopal S, Rajagopal K, Lefkowitz RJ. Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat Rev Drug Discov. 2010; 9(5):373–86. https://doi.org/10.1038/nrd3024 PMID: 20431569; PubMed Central PMCID: PMCPMC2902265.
34. Whalen EJ, Rajagopal S, Lefkowitz RJ. Therapeutic potential of beta-arrestin- and G protein-biased agonists. Trends Mol Med. 2011; 17(3):126–39. https://doi.org/10.1016/j.molmed.2010.11.004 PMID: 21183406; PubMed Central PMCID: PMCPMC3628754.
35. Ogawa S, Watanabe T, Moriyuki K, Goto Y, Yamane S, Watanabe A, et al. Structural optimization and structure-functional selectivity relationship studies of G protein-biased EP2 receptor agonists. Bioorg Med Chem Lett. 2016; 26(10):2446–9. https://doi.org/10.1016/j.bmcl.2016.03.110 PMID: 27055938.
36. Zhou L, Lovell KM, Frankowski KJ, Slauson SR, Phillips AM, Streicher JM, et al. Development of functionally selective, small molecule agonists at kappa opioid receptors. J Biol Chem. 2013; 288 (51):36703–16. https://doi.org/10.1074/jbc.M113.504381 PMID: 24187130; PubMed Central PMCID: PMCPMC3868780.
37. Moller D, Kling RC, Skultety M, Leuner K, Hubner H, Gmeiner P. Functionally selective dopamine D(2), D(3) receptor partial agonists. J Med Chem. 2014; 57(11):4861–75. https://doi.org/10.1021/jm5004039PMID: 24831693.
38. Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, et al. Discovery of beta-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proc Natl Acad Sci U S A. 2011; 108(45):18488–93. https://doi.org/10.1073/pnas.1104807108 PMID: 22025698; PubMed Central PMCID: PMCPMC3215024.
39. Berg KA, Maayani S, Goldfarb J, Clarke WP. Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists. Ann N Y Acad Sci. 1998; 861:104–10. PMID: 9928246.
40. Breivogel CS, Lambert JM, Gerfin S, Huffman JW, Razdan RK. Sensitivity to delta9-tetrahydrocannabi-nol is selectively enhanced in beta-arrestin2 -/- mice. Behav Pharmacol. 2008; 19(4):298–307. https://doi.org/10.1097/FBP.0b013e328308f1e6 PMID: 18622177; PubMed Central PMCID: PMCPMC2751575.
41. Warne T, Moukhametzianov R, Baker JG, Nehme R, Edwards PC, Leslie AG, et al. The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor. Nature. 2011; 469(7329):241–4. https://doi.org/10.1038/nature09746 PMID: 21228877; PubMed Central PMCID: PMCPMC3023143.
42. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015; 14(4):388–405. https://doi.org/10.1016/S1474-4422 (15)70016-5 PMID: 25792098.
43. Heneka MT, O’Banion MK. Inflammatory processes in Alzheimer’s disease. J Neuroimmunol. 2007; 184(1–2):69–91. Epub 2007/01/16. https://doi.org/10.1016/j.jneuroim.2006.11.017 PMID: 17222916.
44. Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull. 2003; 61(3):255–60. PMID: 12909295.
45. Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging. 2007; 28 (4):533–6. https://doi.org/10.1016/j.neurobiolaging.2006.02.012 PMID: 16569464.
46. Janelsins MC, Mastrangelo MA, Oddo S, LaFerla FM, Federoff HJ, Bowers WJ. Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer’s disease mice. J Neuroinflammation. 2005; 2:23. https://doi.org/10.1186/1742-2094-2-23 PMID: 16232318; PubMed Central PMCID: PMCPMC1276812.
47. Grinan-Ferre C, Sarroca S, Ivanova A, Puigoriol-Illamola D, Aguado F, Camins A, et al. Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice. Aging (Albany NY). 2016; 8(4):664–84. https://doi.org/10.18632/aging.100906 PMID: 27013617; PubMed Central PMCID: PMCPMC4925821.
48. Tarkowski E, Andreasen N, Tarkowski A, Blennow K. Intrathecal inflammation precedes development of Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003; 74(9):1200–5. PMID: 12933918; PubMed Central PMCID: PMCPMC1738668. https://doi.org/10.1136/jnnp.74.9.1200
49. Blasko I, Schmitt TL, Steiner E, Trieb K, Grubeck-Loebenstein B. Tumor necrosis factor alpha augments amyloid beta protein (25–35) induced apoptosis in human cells. Neurosci Lett. 1997; 238(1–2):17–20. PMID: 9464644.
50. Yamamoto M, Kiyota T, Horiba M, Buescher JL, Walsh SM, Gendelman HE, et al. Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice. Am J Pathol. 2007; 170(2):680–92. https://doi.org/10.2353/ajpath.2007.060378 PMID: 17255335; PubMed Central PMCID: PMCPMC1851864.
51. Liao YF, Wang BJ, Cheng HT, Kuo LH, Wolfe MS. Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem. 2004; 279(47):49523–32. https://doi.org/10.1074/jbc.M402034200 PMID: 15347683.
52. Kuo LH, Hu MK, Hsu WM, Tung YT, Wang BJ, Tsai WW, et al. Tumor necrosis factor-alpha-elicited stimulation of gamma-secretase is mediated by c-Jun N-terminal kinase-dependent phosphorylation of presenilin and nicastrin. Mol Biol Cell. 2008; 19(10):4201–12. https://doi.org/10.1091/mbc.E07-09-0987PMID: 18667537; PubMed Central PMCID: PMCPMC2555961.
53. Lahiri DK, Chen D, Vivien D, Ge YW, Greig NH, Rogers JT. Role of cytokines in the gene expression of amyloid beta-protein precursor: identification of a 5’-UTR-binding nuclear factor and its implications in Alzheimer’s disease. J Alzheimers Dis. 2003; 5(2):81–90. PMID: 12719626.
54. Koenigsknecht-Talboo J, Landreth GE. Microglial phagocytosis induced by fibrillar beta-amyloid and IgGs are differentially regulated by proinflammatory cytokines. J Neurosci. 2005; 25(36):8240–9. https://doi.org/10.1523/JNEUROSCI.1808-05.2005 PMID: 16148231.
55. Shi JQ, Shen W, Chen J, Wang BR, Zhong LL, Zhu YW, et al. Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res. 2011; 1368:239–47. https://doi.org/10.1016/j.brainres.2010.10.053 PMID: 20971085.
56. McAlpine FE, Lee JK, Harms AS, Ruhn KA, Blurton-Jones M, Hong J, et al. Inhibition of soluble TNF signaling in a mouse model of Alzheimer’s disease prevents pre-plaque amyloid-associated neuropathology. Neurobiol Dis. 2009; 34(1):163–77. PMID: 19320056; PubMed Central PMCID: PMCPMC2948857.
57. Hetier E, Ayala J, Bousseau A, Prochiantz A. Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res. 1991; 86 (2):407–13. PMID: 1684549.
58. Guirao X, Kumar A, Katz J, Smith M, Lin E, Keogh C, et al. Catecholamines increase monocyte TNF receptors and inhibit TNF through beta 2-adrenoreceptor activation. Am J Physiol. 1997; 273(6 Pt 1): E1203–8. PMID: 9435537.
59. Yoshimura T, Kurita C, Nagao T, Usami E, Nakao T, Watanabe S, et al. Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells. Pharmacology. 1997; 54(3):144–52. PMID: 9127437.
60. Parry GC, Mackman N. Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB-mediated transcription. J Immunol. 1997; 159(11):5450–6. PMID: 9548485.
61. Wall EA, Zavzavadjian JR, Chang MS, Randhawa B, Zhu X, Hsueh RC, et al. Suppression of LPS-induced TNF-alpha production in macrophages by cAMP is mediated by PKA-AKAP95-p105. Sci Signal. 2009; 2(75):ra28. https://doi.org/10.1126/scisignal.2000202 PMID: 19531803; PubMed Central PMCID: PMCPMC2770900.
62. Ollivier V, Parry GC, Cobb RR, de Prost D, Mackman N. Elevated cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytic cells and endothelial cells. J Biol Chem. 1996; 271(34):20828–35. PMID: 8702838.
63. Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacology. 1999; 38(6):735–67. PMID: 10465680.
64. Geerts H, Guillaumat PO, Grantham C, Bode W, Anciaux K, Sachak S. Brain levels and acetylcholines-terase inhibition with galantamine and donepezil in rats, mice, and rabbits. Brain Res. 2005; 1033 (2):186–93. https://doi.org/10.1016/j.brainres.2004.11.042 PMID: 15694923.