U.S. Department of Health and Human Services
Kenneth Jacobson

 Contact Info

Tel: 301-496-9024
Email: kajacobs@helix.nih.gov

 Select Experience

  • Bantrel FellowWeizmann Institute of Science, Department of Organic Chemistry1983
  • Ph.D.University of California, San Diego1981
  • M.S.University of California, San Diego1978
  • B.A.Reed College1975

 Related Links


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

Section Chief, Molecular Recognition SectionLaboratory of Bioorganic Chemistry
  • Chemistry/Chemical Biology
  • Molecular Biology/Biochemistry
  • Molecular Pharmacology/Toxicology


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

Janowsky A, Tosh DK, Eshleman AJ, Jacobson KA. Rigid Adenine Nucleoside Derivatives as Novel Modulators of the Human Sodium Symporters for Dopamine and Norepinephrine. J Pharmacol Exp Ther. 2016 Jan 26; 357 (2016 Jan 26; 357; 1):24-35. [Full Text/Abstract]
Jacobson KA. New paradigms in GPCR drug discovery. Biochem Pharmacol. 2015 Aug 8; 98 (98; 4; 2015 Aug 8):541-555. [Full Text/Abstract]
Ford A, Castonguay A, Cottet M, Little JW, Chen Z, Symons-Liguori AM, Doyle T, Egan TM, Vanderah TW, De Koninck Y, Tosh DK, Jacobson KA, Salvemini D. Engagement of the GABA to KCC2 signaling pathway contributes to the analgesic effects of A3AR agonists in neuropathic pain. J Neurosci. 2015 Apr 15; 35 (35; 15; 2015 Apr 15):6057-67. [Full Text/Abstract]
Jacobson KA, Paoletta S, Katritch V, Wu B, Gao ZG, Zhao Q, Stevens RC, Kiselev E. Nucleotides Acting at P2Y Receptors: Connecting Structure and Function. Mol Pharmacol. 2015 Apr 2; 88 (2; 2015 Apr 2; 88):220-30. [Full Text/Abstract]
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. Two disparate ligand-binding sites in the human P2Y1 receptor. Nature. 2015 Mar 30; 520 (520; 2015 Mar 30; 7547):317-21. [Full Text/Abstract]
Tosh DK, Finley A, Paoletta S, Moss SM, Gao ZG, Gizewski ET, Auchampach JA, Salvemini D, Jacobson KA. In vivo phenotypic screening for treating chronic neuropathic pain: modification of c2-arylethynyl group of conformationally constrained a3 adenosine receptor agonists. J Med Chem. 2014 Nov 25; 57 (2014 Nov 25; 23; 57):9901-14. [Full Text/Abstract]
Jacobson KA, Costanzi S, Paoletta S. Computational studies to predict or explain G protein coupled receptor polypharmacology. Trends Pharmacol Sci. 2014 Nov 14; 35 (35; 2014 Nov 14; 12):658-63. [Full Text/Abstract]
Ciruela F, Jacobson KA, Fernández-Dueñas V. Portraying g protein-coupled receptors with fluorescent ligands. ACS Chem Biol. 2014 Jul 28; 9 (2014 Jul 28; 9):1918-28. [Full Text/Abstract]
Leung CT, Li A, Banerjee J, Gao ZG, Kambayashi T, Jacobson KA, Civan MM. The role of activated adenosine receptors in degranulation of human LAD2 mast cells. Purinergic Signal. 2014 Mar 5; 10 (2014 Mar 5; 10; 3):465-75. [Full Text/Abstract]
Gao ZG, Balasubramanian R, Kiselev E, Wei Q, Jacobson KA. Probing Biased/Partial Agonism at the G Protein-Coupled A2B Adenosine Receptoř. Biochem Pharmacol. 2014 Aug 1; 90 (2014 Aug 1; 3; 90):297-306. [Full Text/Abstract]
Toti KS, Moss SM, Paoletta S, Gao ZG, Jacobson KA, Van Calenbergh S. Synthesis and evaluation of N⁶-substituted apioadenosines as potential adenosine A₃ receptor modulators. Bioorg Med Chem. 2014 Aug 1; 22 (15; 2014 Aug 1; 22):4257-68. [Full Text/Abstract]
Tosh DK, Paoletta S, Chen Z, Moss SM, Gao ZG, Salvemini D, Jacobson KA. Extended N6 substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor. Bioorg Med Chem Lett. 2014 Aug 1; 24 (15; 2014 Aug 1; 24):3302-6. [Full Text/Abstract]
Ochoa-Cortes F, Liñán-Rico A, Jacobson KA, Christofi FL. Potential for Developing Purinergic Drugs for Gastrointestinal Diseases. Inflamm Bowel Dis. 2014 Jul; 20 (20; 7; 2014 Jul):1259-87. [Full Text/Abstract]
Jayasekara PS, Barrett MO, Ball CB, Brown KA, Hammes E, Balasubramanian R, Harden TK, Jacobson KA. 4-Alkyloxyimino Derivatives of Uridine-5'-triphosphate: Distal Modification of Potent Agonists as a Strategy for Molecular Probes of P2Y2, P2Y4, and P2Y6 Receptors. J Med Chem. 2014 May 8; 57 (9; 2014 May 8; 57):3874-83. [Full Text/Abstract]
Zhang K, Zhang J, Gao ZG, Zhang D, Zhu L, Han GW, Moss SM, Paoletta S, Kiselev E, Lu W, Fenalti G, Zhang W, Müller CE, Yang H, Jiang H, Cherezov V, Katritch V, Jacobson KA, Stevens RC, Wu B, Zhao Q. Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature. 2014 May 1; 509 (2014 May 1; 509; 7498):115-8. [Full Text/Abstract]
Zhang J, Zhang K, Gao ZG, Paoletta S, Zhang D, Han GW, Li T, Ma L, Zhang W, Müller CE, Yang H, Jiang H, Cherezov V, Katritch V, Jacobson KA, Stevens RC, Wu B, Zhao Q. Agonist-bound structure of the human P2Y12 receptor. Nature. 2014 May 1; 509 (2014 May 1; 509; 7498):119-122. [Full Text/Abstract]
Yang T, Shen JB, Yang R, Redden J, Dodge-Kafka K, Grady J, Jacobson KA, Liang BT. A Novel Protective Role of Endogenous Cardiac Myocyte P2X4 Receptors in Heart Failure. Circ Heart Fail. 2014 May; 7 (7; 2014 May; 3):510-8. [Full Text/Abstract]
Nayak A, Chandra G, Hwang I, Kim K, Hou X, Kim HO, Sahu PK, Roy KK, Yoo J, Lee Y, Cui M, Choi S, Moss SM, Phan K, Gao ZG, Ha H, Jacobson KA, Jeong LS. Synthesis and anti-renal fibrosis activity of conformationally locked truncated 2-hexynyl-N(6)-substituted-(N)-methanocarba-nucleosides as A3 adenosine receptor antagonists and partial agonists. J Med Chem. 2014 Feb 27; 57 (4; 2014 Feb 27; 57):1344-54. [Full Text/Abstract]
Balasubramanian R, Robaye B, Boeynaems JM, Jacobson KA. Enhancement of glucose uptake in mouse skeletal muscle cells and adipocytes by P2Y6 receptor agonists. PLoS One. 2014 Dec 30; 9 (12; 9; 2014 Dec 30):e116203. [Full Text/Abstract]
Jacobson KA. Crystal structures of the A2A adenosine receptor and their use in medicinal chemistry. In Silico Pharmacol. 2013 Dec 20; 1 (2013 Dec 20; 1):22. [Full Text/Abstract]
Tosh DK, Paoletta S, Deflorian F, Phan K, Moss SM, Gao ZG, Jiang X, Jacobson KA. Structural sweet spot for A1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: receptor docking and potent anticonvulsant activity. J Med Chem. 2012 Sep 27; 55 (2012 Sep 27; 55; 18):8075-90. [Full Text/Abstract]
Jacobson KA, Costanzi S. New insights for drug design from the X-ray crystallographic structures of G-protein-coupled receptors. Mol Pharmacol. 2012 Sep; 82 (2012 Sep; 82; 3):361-71. [Full Text/Abstract]
Tosh DK, Phan K, Gao ZG, Gakh AA, Xu F, Deflorian F, Abagyan R, Stevens RC, Jacobson KA, Katritch V. Optimization of adenosine 5'-carboxamide derivatives as adenosine receptor agonists using structure-based ligand design and fragment screening. J Med Chem. 2012 May 10; 55 (55; 9; 2012 May 10):4297-308. [Full Text/Abstract]
Chen Z, Janes K, Chen C, Doyle T, Bryant L, Tosh DK, Jacobson KA, Salvemini D. Controlling murine and rat chronic pain through A3 adenosine receptor activation. FASEB J. 2012 May; 26 (2012 May; 5; 26):1855-65. [Full Text/Abstract]
Fishman P, Bar-Yehuda S, Liang BT, Jacobson KA. Pharmacological and therapeutic effects of A3 adenosine receptor agonists. Drug Discov Today. 2012 Apr; 17 (17; 2012 Apr; 7-8):359-66. [Full Text/Abstract]
Kecskés A, Tosh DK, Wei Q, Gao ZG, Jacobson KA. GPCR ligand dendrimer (GLiDe) conjugates: adenosine receptor interactions of a series of multivalent xanthine antagonists. Bioconjug Chem. 2011 Jun 15; 22 (6; 2011 Jun 15; 22):1115-27. [Full Text/Abstract]
Xu F, Wu H, Katritch V, Han GW, Jacobson KA, Gao ZG, Cherezov V, Stevens RC. Structure of an agonist-bound human A2A adenosine receptor. Science. 2011 Apr 15; 332 (6027; 2011 Apr 15; 332):322-7. [Full Text/Abstract]
Jacobson KA, Boeynaems JM. P2Y nucleotide receptors: promise of therapeutic applications. Drug Discov Today. 2010 Jul; 15 (2010 Jul; 15; 13-14):570-8. [Full Text/Abstract]
Carlsson J, Yoo L, Gao ZG, Irwin JJ, Shoichet BK, Jacobson KA. Structure-based discovery of A2A adenosine receptor ligands. J Med Chem. 2010 May 13; 53 (9; 2010 May 13; 53):3748-55. [Full Text/Abstract]
Ivanov AA, Barak D, Jacobson KA. Evaluation of homology modeling of G-protein-coupled receptors in light of the A(2A) adenosine receptor crystallographic structure. J Med Chem. 2009 May 28; 52 (2009 May 28; 10; 52):3284-92. [Full Text/Abstract]
Klutz AM, Gao ZG, Lloyd J, Shainberg A, Jacobson KA. Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates. J Nanobiotechnology. 2008 Oct 23; 6 (6; 2008 Oct 23):12. [Full Text/Abstract]
Ivanov AA, Jacobson KA. Molecular modeling of a PAMAM-CGS21680 dendrimer bound to an A2A adenosine receptor homodimer. Bioorg Med Chem Lett. 2008 Aug 1; 18 (2008 Aug 1; 15; 18):4312-5. [Full Text/Abstract]
Kim Y, Klutz AM, Jacobson KA. Systematic investigation of polyamidoamine dendrimers surface-modified with poly(ethylene glycol) for drug delivery applications: synthesis, characterization, and evaluation of cytotoxicity. Bioconjug Chem. 2008 Aug; 19 (8; 19; 2008 Aug):1660-72. [Full Text/Abstract]
Jeong LS, Lee HW, Kim HO, Tosh DK, Pal S, Choi WJ, Gao ZG, Patel AR, Williams W, Jacobson KA, Kim HD. Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists. Bioorg Med Chem Lett. 2008 Mar 1; 18 (2008 Mar 1; 5; 18):1612-6. [Full Text/Abstract]
Gao ZG, Jacobson KA. Emerging adenosine receptor agonists. Expert Opin Emerg Drugs. 2007 Sep; 12 (12; 3; 2007 Sep):479-92. [Full Text/Abstract]
Ko H, Fricks I, Ivanov AA, Harden TK, Jacobson KA. Structure-activity relationship of uridine 5'-diphosphoglucose analogues as agonists of the human P2Y14 receptor. J Med Chem. 2007 May 3; 50 (50; 9; 2007 May 3):2030-9. [Full Text/Abstract]
Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, Inoue K. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature. 2007 Apr 26; 446 (7139; 2007 Apr 26; 446):1091-5. [Full Text/Abstract]
Jacobson KA, Gao ZG, Liang BT. Neoceptors: reengineering GPCRs to recognize tailored ligands. Trends Pharmacol Sci. 2007 Mar; 28 (28; 3; 2007 Mar):111-6. [Full Text/Abstract]
Gao ZG, Jacobson KA. Keynote review: allosterism in membrane receptors. Drug Discov Today. 2006 Mar; 11 (2006 Mar; 5-6; 11):191-202. [Full Text/Abstract]
Jacobson KA, Gao ZG. Adenosine receptors as therapeutic targets. Nat Rev Drug Discov. 2006 Mar; 5 (2006 Mar; 3; 5):247-64. [Full Text/Abstract]
Gao ZG, Kim SK, Ijzerman AP, Jacobson KA. Allosteric modulation of the adenosine family of receptors. Mini Rev Med Chem. 2005 Jun; 5 (6; 2005 Jun; 5):545-53. [Full Text/Abstract]
Jacobson KA, Ohno M, Duong HT, Kim SK, Tchilibon S, Cesnek M, Holý A, Gao ZG. A neoceptor approach to unraveling microscopic interactions between the human A2A adenosine receptor and its agonists. Chem Biol. 2005 Feb; 12 (2005 Feb; 2; 12):237-47. [Full Text/Abstract]
Joshi BV, Moon HR, Fettinger JC, Marquez VE, Jacobson KA. A new synthetic route to (North)-methanocarba nucleosides designed as A3 adenosine receptor agonists. J Org Chem. 2005 Jan 21; 70 (2005 Jan 21; 2; 70):439-47. [Full Text/Abstract]
Kim HS, Ohno M, Xu B, Kim HO, Choi Y, Ji XD, Maddileti S, Marquez VE, Harden TK, Jacobson KA. 2-Substitution of adenine nucleotide analogues containing a bicyclo[3.1.0]hexane ring system locked in a northern conformation: enhanced potency as P2Y1 receptor antagonists. J Med Chem. 2003 Nov 6; 46 (46; 2003 Nov 6; 23):4974-87. [Full Text/Abstract]