Kenneth A. Jacobson, Ph.D., John W. Daly Distinguished Investigator

Photo of Kenneth Jacobson
Scientific Focus Areas: Chemical Biology, Molecular Biology and Biochemistry, Molecular Pharmacology, Structural Biology

Publications

A selection of recent and significant publications can be viewed below.

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In vivo phenotypic screening for treating chronic neuropathic pain: modification of C2-arylethynyl group of conformationally constrained A3 adenosine receptor agonists.
Tosh DK, Finley A, Paoletta S, Moss SM, Gao ZG, Gizewski ET, Auchampach JA, Salvemini D, Jacobson KA.
J Med Chem (2014 Dec 11) 57:9901-14. Abstract/Full Text
Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states.
Little JW, Ford A, Symons-Liguori AM, Chen Z, Janes K, Doyle T, Xie J, Luongo L, Tosh DK, Maione S, Bannister K, Dickenson AH, Vanderah TW, Porreca F, Jacobson KA, Salvemini D.
Brain (2015 Jan) 138:28-35. Abstract/Full Text
Remote control of movement disorders using a photoactive adenosine A2A receptor antagonist.
Taura J, Nolen EG, Cabré G, Hernando J, Squarcialupi L, López-Cano M, Jacobson KA, Fernández-Dueñas V, Ciruela F.
J Control Release (2018 Aug 10) 283:135-142. Abstract/Full Text
Two disparate ligand-binding sites in the human P2Y1 receptor.
Zhang D, Gao ZG, Zhang K, Kiselev E, Crane S, Wang J, Paoletta S, Yi C, Ma L, Zhang W, Han GW, Liu H, Cherezov V, Katritch V, Jiang H, Stevens RC, Jacobson KA, Zhao Q, Wu B.
Nature (2015 Apr 16) 520:317-21. Abstract/Full Text
Structure-Based Design of 3-(4-Aryl-1H-1,2,3-triazol-1-yl)-Biphenyl Derivatives as P2Y14 Receptor Antagonists.
Junker A, Balasubramanian R, Ciancetta A, Uliassi E, Kiselev E, Martiriggiano C, Trujillo K, Mtchedlidze G, Birdwell L, Brown KA, Harden TK, Jacobson KA.
J Med Chem (2016 Jul 14) 59:6149-68. Abstract/Full Text

Additional Publications

Activation of adenosine A2A or A2B receptors causes hypothermia in mice.
Carlin JL, Jain S, Duroux R, Suresh RR, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML.
Neuropharmacology (2018 Sep 1) 139:268-278. Abstract/Full Text
Author Correction: Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors.
Liu X, Gao ZG, Wu Y, Stevens RC, Jacobson KA, Zhao S.
Sci Rep (2018 Jul 24) 8:11380. Abstract/Full Text
Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice.
Yang C, Larin A, McKenna JT, Jacobson KA, Winston S, Strecker RE, Kalinchuk A, Basheer R, Brown RE.
Sci Rep (2018 Jul 16) 8:10730. Abstract/Full Text
Extrinsic Tryptophans as NMR Probes of Allosteric Coupling in Membrane Proteins: Application to the A2A Adenosine Receptor.
Eddy MT, Gao ZG, Mannes P, Patel N, Jacobson KA, Katritch V, Stevens RC, Wüthrich K.
J Am Chem Soc (2018 Jul 5) 140:8228-8235. Abstract/Full Text
Thermostabilization and purification of the human dopamine transporter (hDAT) in an inhibitor and allosteric ligand bound conformation.
Navratna V, Tosh DK, Jacobson KA, Gouaux E.
PLoS One (2018) 13:e0200085. Abstract/Full Text
A3 Adenosine Receptors as Modulators of Inflammation: From Medicinal Chemistry to Therapy.
Jacobson KA, Merighi S, Varani K, Borea PA, Baraldi S, Aghazadeh Tabrizi M, Romagnoli R, Baraldi PG, Ciancetta A, Tosh DK, Gao ZG, Gessi S.
Med Res Rev (2018 Jul) 38:1031-1072. Abstract/Full Text
A binding kinetics study of human adenosine A3 receptor agonists.
Xia L, Kyrizaki A, Tosh DK, van Duijl TT, Roorda JC, Jacobson KA, IJzerman AP, Heitman LH.
Biochem Pharmacol (2018 Jul) 153:248-259. Abstract/Full Text
Structure-Guided Modification of Heterocyclic Antagonists of the P2Y14 Receptor.
Yu J, Ciancetta A, Dudas S, Duca S, Lottermoser J, Jacobson KA.
J Med Chem (2018 Jun 14) 61:4860-4882. Abstract/Full Text
Chemotherapy-induced pain is promoted by enhanced spinal adenosine kinase levels through astrocyte-dependent mechanisms.
Wahlman C, Doyle TM, Little JW, Luongo L, Janes K, Chen Z, Esposito E, Tosh DK, Cuzzocrea S, Jacobson KA, Salvemini D.
Pain (2018 Jun) 159:1025-1034. Abstract/Full Text
Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors.
Liu X, Gao ZG, Wu Y, Stevens RC, Jacobson KA, Zhao S.
Sci Rep (2018 May 24) 8:8084. Abstract/Full Text
On the G protein-coupling selectivity of the native A2B adenosine receptor.
Gao ZG, Inoue A, Jacobson KA.
Biochem Pharmacol (2018 May) 151:201-213. Abstract/Full Text
Species differences and mechanism of action of A3 adenosine receptor allosteric modulators.
Du L, Gao ZG, Paoletta S, Wan TC, Gizewski ET, Barbour S, van Veldhoven JPD, IJzerman AP, Jacobson KA, Auchampach JA.
Purinergic Signal (2018 Mar) 14:59-71. Abstract/Full Text
Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling.
White KL, Eddy MT, Gao ZG, Han GW, Lian T, Deary A, Patel N, Jacobson KA, Katritch V, Stevens RC.
Structure (2018 Feb 6) 26:259-269.e5. Abstract/Full Text
Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine Receptor.
Eddy MT, Lee MY, Gao ZG, White KL, Didenko T, Horst R, Audet M, Stanczak P, McClary KM, Han GW, Jacobson KA, Stevens RC, Wüthrich K.
Cell (2018 Jan 11) 172:68-80.e12. Abstract/Full Text
Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.
Ciancetta A, Jacobson KA.
Methods Mol Biol (2018) 1705:45-72. Abstract/Full Text
Demystifying P2Y1 Receptor Ligand Recognition through Docking and Molecular Dynamics Analyses.
Ciancetta A, O'Connor RD, Paoletta S, Jacobson KA.
J Chem Inf Model (2017 Dec 26) 57:3104-3123. Abstract/Full Text
Purinergic Signaling in Mast Cell Degranulation and Asthma.
Gao ZG, Jacobson KA.
Front Pharmacol (2017) 8:947. Abstract/Full Text
Polypharmacology of conformationally locked methanocarba nucleosides.
Jacobson KA, Tosh DK, Toti KS, Ciancetta A.
Drug Discov Today (2017 Dec) 22:1782-1791. Abstract/Full Text
Purinergic drug targets for gastrointestinal disorders.
Burnstock G, Jacobson KA, Christofi FL.
Curr Opin Pharmacol (2017 Dec) 37:131-141. Abstract/Full Text
Distinct Signaling Patterns of Allosteric Antagonism at the P2Y1 Receptor.
Gao ZG, Jacobson KA.
Mol Pharmacol (2017 Nov) 92:613-626. Abstract/Full Text
Pyrimidine Nucleotides Containing a (S)-Methanocarba Ring as P2Y6 Receptor Agonists.
Toti KS, Jain S, Ciancetta A, Balasubramanian R, Chakraborty S, Surujdin R, Shi ZD, Jacobson KA.
Medchemcomm (2017 Oct 1) 8:1897-1908. Abstract/Full Text
Polypharmacology of N6-(3-Iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) and Related A3 Adenosine Receptor Ligands: Peroxisome Proliferator Activated Receptor (PPAR) γ Partial Agonist and PPARδ Antagonist Activity Suggests Their Antidiabetic Potential.
Yu J, Ahn S, Kim HJ, Lee M, Ahn S, Kim J, Jin SH, Lee E, Kim G, Cheong JH, Jacobson KA, Jeong LS, Noh M.
J Med Chem (2017 Sep 14) 60:7459-7475. Abstract/Full Text
Highly selective A3 adenosine receptor agonists relieve chronic neuropathic pain.
Salvemini D, Jacobson KA.
Expert Opin Ther Pat (2017 Aug) 27:967. Abstract/Full Text
Bitopic fluorescent antagonists of the A2A adenosine receptor based on pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine functionalized congeners.
Duroux R, Ciancetta A, Mannes P, Yu J, Boyapati S, Gizewski E, Yous S, Ciruela F, Auchampach JA, Gao ZG, Jacobson KA.
Medchemcomm (2017 Aug 1) 8:1659-1667. Abstract/Full Text
Fragment optimization for GPCRs by molecular dynamics free energy calculations: Probing druggable subpockets of the A 2A adenosine receptor binding site.
Matricon P, Ranganathan A, Warnick E, Gao ZG, Rudling A, Lambertucci C, Marucci G, Ezzati A, Jaiteh M, Dal Ben D, Jacobson KA, Carlsson J.
Sci Rep (2017 Jul 25) 7:6398. Abstract/Full Text
Exploring the Role of N6-Substituents in Potent Dual Acting 5'-C-Ethyltetrazolyladenosine Derivatives: Synthesis, Binding, Functional Assays, and Antinociceptive Effects in Mice ∇.
Petrelli R, Scortichini M, Kachler S, Boccella S, Cerchia C, Torquati I, Del Bello F, Salvemini D, Novellino E, Luongo L, Maione S, Jacobson KA, Lavecchia A, Klotz KN, Cappellacci L.
J Med Chem (2017 May 25) 60:4327-4341. Abstract/Full Text
N6-Substituted 5'-N-Methylcarbamoyl-4'-selenoadenosines as Potent and Selective A3 Adenosine Receptor Agonists with Unusual Sugar Puckering and Nucleobase Orientation.
Yu J, Zhao LX, Park J, Lee HW, Sahu PK, Cui M, Moss SM, Hammes E, Warnick E, Gao ZG, Noh M, Choi S, Ahn HC, Choi J, Jacobson KA, Jeong LS.
J Med Chem (2017 Apr 27) 60:3422-3437. Abstract/Full Text
Scaffold Repurposing of Nucleosides (Adenosine Receptor Agonists): Enhanced Activity at the Human Dopamine and Norepinephrine Sodium Symporters.
Tosh DK, Janowsky A, Eshleman AJ, Warnick E, Gao ZG, Chen Z, Gizewski E, Auchampach JA, Salvemini D, Jacobson KA.
J Med Chem (2017 Apr 13) 60:3109-3123. Abstract/Full Text
Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding.
Ciancetta A, Jacobson KA.
Molecules (2017 Mar 11) 22. Abstract/Full Text
Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms.
Carlin JL, Jain S, Gizewski E, Wan TC, Tosh DK, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML.
Neuropharmacology (2017 Mar 1) 114:101-113. Abstract/Full Text
Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HT2B/5HT2C Serotonin Receptor Antagonists.
Tosh DK, Ciancetta A, Warnick E, Crane S, Gao ZG, Jacobson KA.
J Med Chem (2016 Dec 22) 59:11006-11026. Abstract/Full Text
UDP-glucose promotes neutrophil recruitment in the lung.
Sesma JI, Weitzer CD, Livraghi-Butrico A, Dang H, Donaldson S, Alexis NE, Jacobson KA, Harden TK, Lazarowski ER.
Purinergic Signal (2016 Dec) 12:627-635. Abstract/Full Text
Inherited dysfunctional platelet P2Y12 receptor mutations associated with bleeding disorders.
Lecchi A, Femia EA, Paoletta S, Dupuis A, Ohlmann P, Gachet C, Jacobson KA, Machura K, Podda GM, Zieger B, Cattaneo M.
Hamostaseologie (2016 Nov 7) 36:279-283. Abstract/Full Text
Structure-Based Screening of Uncharted Chemical Space for Atypical Adenosine Receptor Agonists.
Rodríguez D, Chakraborty S, Warnick E, Crane S, Gao ZG, O'Connor R, Jacobson KA, Carlsson J.
ACS Chem Biol (2016 Oct 21) 11:2763-2772. Abstract/Full Text
Ocular Purine Receptors as Drug Targets in the Eye.
Jacobson KA, Civan MM.
J Ocul Pharmacol Ther (2016 Oct) 32:534-547. Abstract/Full Text
South (S)- and North (N)-Methanocarba-7-Deazaadenosine Analogues as Inhibitors of Human Adenosine Kinase.
Toti KS, Osborne D, Ciancetta A, Boison D, Jacobson KA.
J Med Chem (2016 Jul 28) 59:6860-77. Abstract/Full Text
Structure-Activity Analysis of Biased Agonism at the Human Adenosine A3 Receptor.
Baltos JA, Paoletta S, Nguyen AT, Gregory KJ, Tosh DK, Christopoulos A, Jacobson KA, May LT.
Mol Pharmacol (2016 Jul) 90:12-22. Abstract/Full Text
Medicinal chemistry of adenosine, P2Y and P2X receptors.
Jacobson KA, Müller CE.
Neuropharmacology (2016 May) 104:31-49. Abstract/Full Text
On the selectivity of the Gαq inhibitor UBO-QIC: A comparison with the Gαi inhibitor pertussis toxin.
Gao ZG, Jacobson KA.
Biochem Pharmacol (2016 May 1) 107:59-66. Abstract/Full Text
Purine (N)-Methanocarba Nucleoside Derivatives Lacking an Exocyclic Amine as Selective A3 Adenosine Receptor Agonists.
Tosh DK, Ciancetta A, Warnick E, O'Connor R, Chen Z, Gizewski E, Crane S, Gao ZG, Auchampach JA, Salvemini D, Jacobson KA.
J Med Chem (2016 Apr 14) 59:3249-63. Abstract/Full Text
Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics.
Janes K, Symons-Liguori AM, Jacobson KA, Salvemini D.
Br J Pharmacol (2016 Apr) 173:1253-67. Abstract/Full Text
Rigid Adenine Nucleoside Derivatives as Novel Modulators of the Human Sodium Symporters for Dopamine and Norepinephrine.
Janowsky A, Tosh DK, Eshleman AJ, Jacobson KA.
J Pharmacol Exp Ther (2016 Apr) 357:24-35. Abstract/Full Text
Peripheral Adenosine A3 Receptor Activation Causes Regulated Hypothermia in Mice That Is Dependent on Central Histamine H1 Receptors.
Carlin JL, Tosh DK, Xiao C, Piñol RA, Chen Z, Salvemini D, Gavrilova O, Jacobson KA, Reitman ML.
J Pharmacol Exp Ther (2016 Feb) 356:474-82. Abstract/Full Text
Characterization of Polyamidoamino (PAMAM) Dendrimers Using In-Line Reversed Phase LC Electrospray Ionization Mass Spectrometry.
Lloyd JR, Jayasekara PS, Jacobson KA.
Anal Methods (2016 Jan 14) 8:263-269. Abstract/Full Text
New paradigms in GPCR drug discovery.
Jacobson KA.
Biochem Pharmacol (2015 Dec 15) 98:541-55. Abstract/Full Text