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

Section Chief: Molecular Recognition Section, Laboratory of Bioorganic Chemistry

Scientific Focus Areas: Chemical Biology, Molecular Biology and Biochemistry, Molecular Pharmacology, Structural Biology, Cell Biology

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Publications

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

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Structure of the human dopamine transporter and mechanisms of inhibition.: Srivastava DK, Navratna V, Tosh DK, Chinn A, Sk MF, Tajkhorshid E, Jacobson KA, Gouaux E.; Nature (2024 Aug) 632:672-677. Abstract/Full Text
Bitopic A(3) Adenosine Receptor Molecular Probes: Positive Allosteric Modulation and Noncanonical Activation.: Kurma SH, Pavan M, Wan TC, Pradhan B, López-Cano M, Ciruela F, Gao ZG, Auchampach JA, Jacobson KA.; J Med Chem (2025 Oct 9) 68:20717-20740. Abstract/Full Text
Alicyclic Ring Size Variation of 4-Phenyl-2-naphthoic Acid Derivatives as P2Y(14) Receptor Antagonists.: Wen Z, Pramanik A, Lewicki SA, Jung YH, Gao ZG, Randle JCR, Cronin C, Chen Z, Giancotti LA, Whitehead GS, Liang BT, Breton S, Salvemini D, Cook DN, Jacobson KA.; J Med Chem (2023 Jul 13) 66:9076-9094. Abstract/Full Text
2-Substituted (N)-Methanocarba A(3) Adenosine Receptor Agonists: In Silico, In Vitro, and In Vivo Characterization.: Tosh DK, Pavan M, Cronin C, Pottie E, Wan TC, Chen E, Lewicki SA, Campbell RG, Gao ZG, Auchampach JA, Stove CP, Liang BT, Jacobson KA.; ACS Pharmacol Transl Sci (2024 Jul 12) 7:2154-2173. Abstract/Full Text
Adipocyte P2Y14 receptors play a key role in regulating whole-body glucose and lipid homeostasis.: Jain S, Pydi SP, Jung YH, Scortichini M, Kesner EL, Karcz TP, Cook DN, Gavrilova O, Wess J, Jacobson KA.; JCI Insight (2021 May 24) 6. Abstract/Full Text

Additional Publications

The long march towards testing the adenosine receptor agonism hypothesis for human cerebroprotection: The story of the A(1)R/A(3)R receptor agonist AST-004.: Liston TE, Korinek WS, Jacobson KA, Lechleiter JD.; Purinergic Signal (2026 May 12) 22. Abstract/Full Text
Fluorine-18-Labeled Nucleotide Analogs Targeting Ecto-5'-Nucleotidase (CD73) for Positron Emission Tomography Imaging of Solid Tumors.: Dobelmann C, Schmies CC, Rolshoven GW, Scortichini M, Wagner S, Isaak A, Idris RM, Dabel J, Grey L, Losenkova K, Moschütz S, Hroub HA, Keim A, Höppner S, Sandholm J, Boström P, Hollmén M, Sträter N, Hermann S, Yegutkin GG, Jacobson KA, Schelhaas S, Müller CE, Junker A.; Angew Chem Int Ed Engl (2026 Apr 20) 65:e22758. Abstract/Full Text
Methodological guidelines for P2X receptor assays and data interpretation.: Gorecki DC, Adinolfi E, Adriouch S, Coutinho-Silva R, Engel T, Gölöncsér F, Haag F, Illes P, Jacobson KA, Koch-Nolte F, Mansoor SE, Matute C, Melino G, Novak I, Pegoraro A, Pelegrin P, Piacentini M, Robson SC, Rumney RMH, Seman M, Sluyter R, Sperlagh B, Tang Y, Tarantini M, Ulrich H, Vouret-Craviari V, Ye Q, Yegutkin GG, Verkhratsky A.; Cell Death Dis (2026 Apr 20) 17. Abstract/Full Text
(N)-Methanocarba Adenosine Derivatives as Dual Modulators of P-Glycoprotein and ABCG2 Transporters.: Murakami M, Tosh DK, Salazar PB, Jacobson KA, Ambudkar SV.; J Med Chem (2026 Feb 26) 69:4945-4968. Abstract/Full Text
(N)-Methanocarba-adenosines as monoamine transporter allosteric inhibitors: Extended N(6) groups for bitopic stabilization.: Tosh DK, Pavan M, Kozell LB, Eshleman AJ, Schmachtenberg JL, Wolfrum KM, Schutzer WE, Abbas AI, Jacobson KA.; Eur J Med Chem (2026 Jan 5) 301:118167. Abstract/Full Text
UDP-glucose and MRS2905 agonist-bound states of the purinergic P2Y(14) receptor.: Fay JF, Kousouros J, Gao ZG, Pavan M, Oliva P, Pramanik A, Meyer C, Kurma SH, Xu W, Krumm B, Jacobson KA.; Commun Biol (2025 Nov 21) 8:1816. Abstract/Full Text
P2Y(14) Receptor Antagonists: Piperidine Bioisosteres and Mutagenesis-Supported Molecular Modeling.: Pramanik A, Wen Z, Pavan M, Kurma SH, Karcz T, Lewicki SA, Liu N, Demby T, Gavrilova O, Oliva P, Erlitz KS, Junker A, Jung YH, Chen Z, Salvemini D, Kousouros J, Gao ZG, Fay JF, Jacobson KA.; ACS Pharmacol Transl Sci (2025 Sep 12) 8:3126-3148. Abstract/Full Text
Development and Preclinical Evaluation of PET Radiotracers Targeting Adenosine A(1) Receptors.: Bakhoda AG, Pearson TD, Gao ZG, O'Conor KA, Eisenberg SM, Kelleher AC, Kang Y, Liow JS, Choi JY, Kim W, Seo J, Freaney ML, Jacobson KA, Volkow ND, Kim SW.; ACS Med Chem Lett (2025 Jul 10) 16:1365-1372. Abstract/Full Text
A(2B) adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of G(i), G(q), G(s) proteins and protein kinase C.: Gao ZG, Gao RR, Meyer CK, Jacobson KA.; Purinergic Signal (2025 Jun) 21:499-513. Abstract/Full Text
A(2B) adenosine receptor signaling and regulation.: Gao ZG, Haddad M, Jacobson KA.; Purinergic Signal (2025 Apr) 21:201-220. Abstract/Full Text
E. B. Hershberg Award: Taming Inflammation by Tuning Purinergic Signaling.: Jacobson KA.; Acc Chem Res (2025 Mar 18) 58:958-970. Abstract/Full Text
Mitochondrial A(3) Adenosine Receptor as a Mechanism for the Protective Effects of A(3)AR Agonists on Chemotherapy-Induced Neuropathic Pain.: Doyle TM, Janes K, Xiao WH, Kolar GR, Luecke HF, Gratton MA, Tosh DK, Jacobson KA, Bennett GJ, Salvemini D.; J Neurosci (2025 Jan 15) 45. Abstract/Full Text
Photoswitchable Diazocine Derivative for Adenosine A(3) Receptor Activation in Psoriasis.: López-Cano M, Scortichini M, Tosh DK, Salmaso V, Ko T, Salort G, Filgaira I, Soler C, Trauner D, Hernando J, Jacobson KA, Ciruela F.; J Am Chem Soc (2025 Jan 8) 147:874-879. Abstract/Full Text
Potent and Selective Human 5-HT(2B) Serotonin Receptor Antagonists: 4'-Cyano-(N)-methanocarba-adenosines by Synthetic Serendipity.: Tosh DK, Pavan M, Clark AA, Lammers J, Villano S, Marri S, Sgambellone S, Choi S, Lee J, Ivancich MS, Bock HA, Campbell RG, Lewicki SA, Levitan IM, Chen E, Liu N, Demby T, Gavrilova O, Gao ZG, Lucarini L, McCorvy JD, Jacobson KA.; J Med Chem (2024 Dec 12) 67:21264-21291. Abstract/Full Text
Terpenes from Cannabis sativa induce antinociception in a mouse model of chronic neuropathic pain via activation of adenosine A 2A receptors.: Schwarz AM, Keresztes A, Bui T, Hecksel R, Peña A, Lent B, Gao ZG, Gamez-Rivera M, Seekins CA, Chou K, Appel TL, Jacobson KA, Al-Obeidi FA, Streicher JM.; Pain (2024 Nov 1) 165:e145-e161. Abstract/Full Text
Analgesic candidate adenosine A 3 receptors are expressed by perineuronal peripheral macrophages in human dorsal root ganglion and spinal cord microglia.: Sapio MR, Staedtler ES, King DM, Maric D, Jahanipour J, Ghetti A, Jacobson KA, Mannes AJ, Iadarola MJ.; Pain (2024 Oct 1) 165:2323-2343. Abstract/Full Text
Membrane mimetic-dependence of GPCR energy landscapes.: Thakur N, Ray AP, Jin B, Afsharian NP, Lyman E, Gao ZG, Jacobson KA, Eddy MT.; Structure (2024 May 2) 32:523-535.e5. Abstract/Full Text
First Potent Macrocyclic A(3) Adenosine Receptor Agonists Reveal G-Protein and β-Arrestin2 Signaling Preferences.: Tosh DK, Fisher CL, Salmaso V, Wan TC, Campbell RG, Chen E, Gao ZG, Auchampach JA, Jacobson KA.; ACS Pharmacol Transl Sci (2023 Sep 8) 6:1288-1305. 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 A(2A) 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
A(3) 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
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 P2Y(1) and P2Y(12) receptors.: Liu X, Gao ZG, Wu Y, Stevens RC, Jacobson KA, Zhao S.; Sci Rep (2018 May 24) 8:8084. 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 A(2A) 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
Demystifying P2Y(1) 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 P2Y(1) Receptor.: Gao ZG, Jacobson KA.; Mol Pharmacol (2017 Nov) 92:613-626. 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
N(6)-Substituted 5'-N-Methylcarbamoyl-4'-selenoadenosines as Potent and Selective A(3) 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 A(1) and A(3) 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 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
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

Last Reviewed February 2025