Mark D Erion

Summary

Affiliation: Metabasis Therapeutics
Country: USA

Publications

  1. ncbi Adenosine kinase inhibitors. 3. Synthesis, SAR, and antiinflammatory activity of a series of l-lyxofuranosyl nucleosides
    Bheemarao G Ugarkar
    Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, San Diego, California 92121, USA
    J Med Chem 46:4750-60. 2003
  2. doi Fructose-1,6-bisphosphatase inhibitors. 1. Purine phosphonic acids as novel AMP mimics
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 52:2880-98. 2009
  3. ncbi HepDirect prodrugs for targeting nucleotide-based antiviral drugs to the liver
    Mark D Erion
    Metabasis Therapeutics Inc, La Jolla, CA 92037, USA
    Curr Opin Investig Drugs 7:109-17. 2006
  4. ncbi Structure-guided design of AMP mimics that inhibit fructose-1,6-bisphosphatase with high affinity and specificity
    Mark D Erion
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 129:15480-90. 2007
  5. pmc Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index
    Mark D Erion
    Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:15490-5. 2007
  6. ncbi Liver-targeted drug delivery using HepDirect prodrugs
    Mark D Erion
    Research and Development, Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, Building 300, San Diego, CA 92121, USA
    J Pharmacol Exp Ther 312:554-60. 2005
  7. pmc MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes
    Mark D Erion
    Department of Biochemistry, Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, Building 300, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 102:7970-5. 2005
  8. ncbi Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, La Jolla, California 92037, USA
    J Am Chem Soc 129:15491-502. 2007
  9. doi Pradefovir: a prodrug that targets adefovir to the liver for the treatment of hepatitis B
    K Raja Reddy
    Department of Chemistry and Biochemistry, Metabasis Therapeutics Inc, La Jolla, CA 92037, USA
    J Med Chem 51:666-76. 2008
  10. doi Fructose-1,6-bisphosphatase Inhibitors. 2. Design, synthesis, and structure-activity relationship of a series of phosphonic acid containing benzimidazoles that function as 5'-adenosinemonophosphate (AMP) mimics
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 53:441-51. 2010

Collaborators

Detail Information

Publications34

  1. ncbi Adenosine kinase inhibitors. 3. Synthesis, SAR, and antiinflammatory activity of a series of l-lyxofuranosyl nucleosides
    Bheemarao G Ugarkar
    Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, San Diego, California 92121, USA
    J Med Chem 46:4750-60. 2003
    ....
  2. doi Fructose-1,6-bisphosphatase inhibitors. 1. Purine phosphonic acids as novel AMP mimics
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 52:2880-98. 2009
    ..11 and 4.13 are as equipotent as AMP with regard to FBPase inhibition. Furthermore, compound 4.11 inhibited glucose production in primary rat hepatocytes and significantly lowered blood glucose levels in fasted rats...
  3. ncbi HepDirect prodrugs for targeting nucleotide-based antiviral drugs to the liver
    Mark D Erion
    Metabasis Therapeutics Inc, La Jolla, CA 92037, USA
    Curr Opin Investig Drugs 7:109-17. 2006
    ..Preclinical and clinical data for the most advanced HepDirect prodrug, pradefovir, highlight the liver-targeting capability of these prodrugs, and the potential benefit of liver targeting on drug efficacy, safety and viral resistance...
  4. ncbi Structure-guided design of AMP mimics that inhibit fructose-1,6-bisphosphatase with high affinity and specificity
    Mark D Erion
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 129:15480-90. 2007
    ..Accordingly, these results suggest that the AMP site of FBPase may represent a potential drug target for reducing the excessive glucose produced by the gluconeogenesis pathway in patients with type 2 diabetes...
  5. pmc Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index
    Mark D Erion
    Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:15490-5. 2007
    ..These results indicate that targeting TR agonists to the liver has the potential to lower both cholesterol and triglyceride levels with an acceptable safety profile...
  6. ncbi Liver-targeted drug delivery using HepDirect prodrugs
    Mark D Erion
    Research and Development, Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, Building 300, San Diego, CA 92121, USA
    J Pharmacol Exp Ther 312:554-60. 2005
    ....
  7. pmc MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes
    Mark D Erion
    Department of Biochemistry, Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, Building 300, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 102:7970-5. 2005
    ..The findings suggest that potent and specific FBPase inhibitors represent a drug class with potential to treat type 2 diabetes through inhibition of GNG...
  8. ncbi Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, La Jolla, California 92037, USA
    J Am Chem Soc 129:15491-502. 2007
    ..Oral administration of the lead prodrug, MB06322 (30, CS-917), to Zucker Diabetic Fatty rats led to dose-dependent inhibition of gluconeogenesis and endogenous glucose production and consequently to significant blood glucose reduction...
  9. doi Pradefovir: a prodrug that targets adefovir to the liver for the treatment of hepatitis B
    K Raja Reddy
    Department of Chemistry and Biochemistry, Metabasis Therapeutics Inc, La Jolla, CA 92037, USA
    J Med Chem 51:666-76. 2008
    ....
  10. doi Fructose-1,6-bisphosphatase Inhibitors. 2. Design, synthesis, and structure-activity relationship of a series of phosphonic acid containing benzimidazoles that function as 5'-adenosinemonophosphate (AMP) mimics
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 53:441-51. 2010
    ..Intravenous administration of 4.4 to Zucker diabetic fatty rats led to rapid and robust glucose lowering, thereby providing the first evidence that FBPase inhibitors could improve glycemia in animal models of type 2 diabetes...
  11. doi Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, La Jolla, California 92037, United States
    J Med Chem 54:153-65. 2011
    ....
  12. ncbi Design, synthesis, and characterization of a series of cytochrome P(450) 3A-activated prodrugs (HepDirect prodrugs) useful for targeting phosph(on)ate-based drugs to the liver
    Mark D Erion
    Departments of Medicinal Chemistry and Biochemistry, Metabasis Therapeutics, Inc, San Diego, California 92121 USA
    J Am Chem Soc 126:5154-63. 2004
    ....
  13. doi Preclinical pharmacokinetics of a HepDirect prodrug of a novel phosphonate-containing thyroid hormone receptor agonist
    James M Fujitaki
    Department of Biological Sciences, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Drug Metab Dispos 36:2393-403. 2008
    ..Hepatic first-pass extraction and metabolism of MB07811, coupled with possible selective distribution of MB07811-derived MB07344, led to a high degree of liver targeting of MB07344...
  14. ncbi Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in Zucker diabetic fatty rats
    Paul D van Poelje
    Department of Biochemistry, Metabasis Therapeutics, 11119 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Diabetes 55:1747-54. 2006
    ..The studies confirm that excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes and suggest that FBPase inhibitors may provide a future treatment option...
  15. doi Delivery of high levels of anti-proliferative nucleoside triphosphates to CYP3A-expressing cells as a potential treatment for hepatocellular carcinoma
    Deidre A Mackenna
    Departments of Biological Sciences and Medicinal Chemistry, Metabasis Therapeutics Inc, La Jolla, CA 92037, USA
    Cancer Chemother Pharmacol 64:981-91. 2009
    ..The aim of our studies was to explore the utility of CYP3A-activated prodrugs of cytarabine and fludarabine monophosphate for the treatment of HCC...
  16. ncbi Liver-targeted prodrugs of 2'-C-methyladenosine for therapy of hepatitis C virus infection
    Scott J Hecker
    Departments of Biochemistry and Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Med Chem 50:3891-6. 2007
    ..Addition of a 2',3'-carbonate prodrug moiety proved to be a successful strategy, and the 1-(4-pyridyl)-1,3-propanyl prodrug containing a 2',3'-carbonate moiety displayed oral bioavailability of 39%...
  17. doi Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors
    Qun Dang
    Department of Medicinal Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 51:4331-9. 2008
    ..Optimization of the diamide prodrugs of phosphonic acid 2a (MB05032) led to the identification of diamide 8 (MB06322), the first reported orally efficacious FBPase inhibitor...
  18. ncbi Adenosine kinase inhibitors. 6. Synthesis, water solubility, and antinociceptive activity of 5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidines substituted at C4 with glycinamides and related compounds
    Brett C Bookser
    Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, San Diego, California 92121, USA
    J Med Chem 48:7808-20. 2005
    ..However, lethal toxicity in the rat formalin paw model occurred with high doses of 16c, and further work on this series was discontinued...
  19. ncbi Liver targeting of hepatitis-B antiviral lamivudine using the HepDirect prodrug technology
    K Raja Reddy
    Department of Chemistry, Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, Building 300, San Diego, CA 92121, USA
    Nucleosides Nucleotides Nucleic Acids 24:375-81. 2005
    ..A HepDirect prodrug of LMV monophosphate generated 34-fold higher levels of the triphosphate in rat hepatocytes and 320-fold higher triphosphate levels in the liver of treated rats relative to LMV...
  20. doi Synthesis and biological evaluation of a series of liver-selective phosphonic acid thyroid hormone receptor agonists and their prodrugs
    Serge H Boyer
    Departments of Medicinal Chemistry and Biosciences, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 51:7075-93. 2008
    ..4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia...
  21. ncbi Synthesis and characterization of a novel liver-targeted prodrug of cytosine-1-beta-D-arabinofuranoside monophosphate for the treatment of hepatocellular carcinoma
    Serge H Boyer
    Departments of Medicinal Chemistry and Biosciences, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Med Chem 49:7711-20. 2006
    ....
  22. doi Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist
    Edward E Cable
    Metabasis Therapeutics, Inc, La Jolla, CA 92037, USA
    Hepatology 49:407-17. 2009
    ....
  23. ncbi Bis[(para-methoxy)benzyl] phosphonate prodrugs with improved stability and enhanced cell penetration
    Qun Dang
    Department of Chemistry, Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 17:3412-6. 2007
    ..BisPMB NMPA esters (4b and 4c) with significantly improved aqueous stability were identified that also resulted in increased intracellular levels of NMPA following prodrug incubation with primary rat hepatocytes...
  24. ncbi Relative binding affinities of fructose-1,6-bisphosphatase inhibitors calculated using a quantum mechanics-based free energy perturbation method
    M Rami Reddy
    Metabasis Therapeutics Inc, La Jolla, CA 92037, USA
    J Am Chem Soc 129:9296-7. 2007
  25. doi Prodrugs of phosphates and phosphonates
    Scott J Hecker
    Metabasis Therapeutics, Inc, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 51:2328-45. 2008
  26. doi Relative solvation free energies calculated using an ab initio QM/MM-based free energy perturbation method: dependence of results on simulation length
    M Rami Reddy
    Metabasis Therapeutics, Inc, La Jolla, CA 92037, USA
    J Comput Aided Mol Des 23:837-43. 2009
    ..The results from this study suggest that performing one long simulation may be better than averaging results from three different simulations using a shorter simulation length and three different starting configurations...
  27. doi Synthesis of 3'-amino-3'-deoxyguanosine and 3'-amino-3'-deoxyxyloguanosine monophosphate HepDirect prodrugs from guanosine
    Brett C Bookser
    Metabasis Therapeutics, Inc, La Jolla, California, USA
    Nucleosides Nucleotides Nucleic Acids 28:969-86. 2009
    ..These HepDirect prodrugs were demonstrated to activate to their respective NTPs in rat hepatocytes...
  28. ncbi Discovery of fructose-1,6-bisphosphatase inhibitors for the treatment of type 2 diabetes
    Paul D van Poelje
    Department of Biological Sciences, Metabasis Therapeutics Inc, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Drug Discov Devel 10:430-7. 2007
    ..The biological characterization of the most advanced of these drugs, CS-917, is also summarized...
  29. ncbi Adenosine kinase inhibitors. 5. Synthesis, enzyme inhibition, and analgesic activity of diaryl-erythro-furanosyltubercidin analogues
    Serge H Boyer
    Metabasis Therapeutics Inc, 9390 Towne Centre Drive, San Diego, California 92121, USA
    J Med Chem 48:6430-41. 2005
    ....
  30. ncbi Computer-aided drug design strategies used in the discovery of fructose 1, 6-bisphosphatase inhibitors
    M Rami Reddy
    Metabasis Therapeutics, Inc, 9390 Towne Centre Drive, San Diego, CA 92121, USA E mail
    Curr Pharm Des 11:283-94. 2005
    ..The results indicate that the MM based methods and the FEP method are useful in the qualitative and quantitative assessment of relative binding affinities of enzyme inhibitors, respectively, prior to synthesis...
  31. ncbi Free energy calculations to estimate ligand-binding affinities in structure-based drug design
    M Rami Reddy
    RR Labs, Inc, 8013 Los Sabalos Street, San Diego, CA 92126, USA
    Curr Pharm Des 20:3323-37. 2014
    ..A case study for the optimization of inhibitors for the fructose 1,6- bisphosphatase inhibitors has been described. ..
  32. ncbi Ab initio quantum mechanics-based free energy perturbation method for calculating relative solvation free energies
    M Rami Reddy
    Metabasis Therapeutics, 11119 North Torrey Pines Road, La Jolla, California 92037, USA
    J Comput Chem 28:491-4. 2007
    ..Future automation of the method and parallelization of the code for Linux 128/256/512 clusters is expected to enhance the speed and increase its use for drug design and lead optimization...
  33. ncbi Remofovir mesylate: a prodrug of PMEA with improved liver-targeting and safety in rats and monkeys
    Chin Chung Lin
    Valeant Pharmaceuticals International, Costa Mesa, Calif, USA
    Antivir Chem Chemother 15:307-17. 2004
    ..Thus, in rats and non-human primates, remofovir mesylate has liver-targeting properties and is safer than adefovir dipivoxil...
  34. ncbi Modulation of cardiac remodeling by adenosine: in vitro and in vivo effects
    Francisco Villarreal
    Department of Medicine, University of California, San Diego 92103 8412, USA
    Mol Cell Biochem 251:17-26. 2003
    ..In addition new, in vitro and in vivo data will be presented supporting the concept that adenosine exerts actions that may ameliorate adverse cardiac remodeling...