Dr. Deepak  K. Dalvie

Dr. Deepak K. Dalvie

Research Scientist
Pfizer Global R and D, USA


Highest Degree
Ph.D. in Medicinal Chemistry from State University of New York, USA

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Area of Interest:

Biomedical Sciences
100%
Pharmacokinetics
62%
Dynamics
90%
Metabolism
75%
Biotransformation
55%

Education

2006

Ph.D.

State University of New York, USA

Medicinal Chemistry

Selected Publications

  1. Zientek, M.A. and D. Dalvie, 2012. Use of a multistaged time-dependent inhibition assay to assess the impact of intestinal metabolism on drug-drug interaction potential. Drug Metab. Dispos., 40: 467-473.
    PubMed  |  

  2. Smith, D.A. and D. Dalvie, 2012. Why do metabolites circulate? Xenobiotica, 42: 107-126.
    CrossRef  |  PubMed  |  

  3. Kumar, G., R. Weiner, A. Vick, C. Xia, D. Dalvie, K. Bateman and R. Ramanathan, 2012. Boston society's 7th applied pharmaceutical analysis. Bioanalysis, 4: 9-12.
    CrossRef  |  PubMed  |  

  4. Kalgutkar, A.S. and D.K. Dalvie, 2012. Drug discovery for a new generation of covalent drugs. Expert. Opin. Drug Discovery, 7: 561-781.
    CrossRef  |  PubMed  |  Direct Link  |  

  5. Dalvie, D., H. Sun, C. Xiang, Q. Hu, Y. Jiang and P. Kang, 2012. Effect of structural variation on aldehyde oxidase-catalyzed oxidation of zoniporide. Drug Metab. Dispos., 40: 1575-1587.
    CrossRef  |  PubMed  |  

  6. Talakad, J.C., M.B. Shah, G.S. Walker, C. Xiang, J.R. Halpert and D. Dalvie, 2011. Comparison of in vitro metabolism of ticlopidine by human cytochrome P450 2B6 and rabbit cytochrome P450 2B4. Drug Metab. Dispos., 39: 539-550.
    CrossRef  |  PubMed  |  

  7. Johnson, T.W., S.P. Tanis, S.L. Butler, D. Dalvie and D.M. DeLisle et al., 2011. Design and synthesis of novel N-hydroxy-dihydronaphthyridinones as potent and orally bioavailable HIV-1 integrase inhibitors. J. Med. Chem., 54: 3393-3417.
    CrossRef  |  PubMed  |  

  8. Jamieson, J.D., E.B. Smith, D.K. Dalvie, G.J. Stevens and G.M. Yanochko, 2011. Myeloperoxidase-mediated bioactivation of 5-hydroxythiabendazole: A possible mechanism of thiabendazole toxicity. Toxicol. In Vitro, 25: 1061-1066.
    CrossRef  |  PubMed  |  Direct Link  |  

  9. Tanis, S.P., M.B. Plewe, T.W. Johnson, S.L. Butler and D. Dalvie et al., 2010. Azaindole N-methyl hydroxamic acids as HIV-1 integrase inhibitors-II. The impact of physicochemical properties on ADME and PK. Bioorg. Med. Chem. Lett., 20: 7429-7434.
    CrossRef  |  PubMed  |  

  10. Pryde, D.C., D. Dalvie, Q. Hu, P. Jones, R.S. Obach and T.D. Tran, 2010. Aldehyde oxidase: An enzyme of emerging importance in drug discovery. J. Med. Chem., 53: 8441-8460.
    CrossRef  |  PubMed  |  

  11. Lee, C.A., D. Neul, A. Clouser-Roche, D. Dalvie and M.R. Wester et al., 2010. Identification of novel substrates for human cytochrome P450 2J2. Drug Metab. Dispos., 38: 347-356.
    CrossRef  |  PubMed  |  

  12. Dalvie, D., S. Nair, P. Kang and C.M. Loi, 2010. Influence of Aromatic Rings on ADME Properties of Drugs. In: Metabolism, Pharmacokinetics and Toxicity of Functional Groups, Smith, D.A. (Ed.). Royal Society of Chemistry, UK., pp: 275-327.

  13. Dalvie, D., P. Kang, C.M. Loi, L. Goulet and S. Nair, 2010. Influence of Heteroaromatic Rings on ADME Properties of Drugs. In: Metabolism, Pharmacokinetics and Toxicity of Functional Groups, Smith, D.A. (Ed.). Royal Society of Chemistry, UK., pp: 328- 369.

  14. Walker, D., J. Brady, D. Dalvie, J. Davis and M. Dowty et al., 2009. A holistic strategy for characterizing the safety of metabolites through drug discovery and development. Chem. Res. Toxicol., 22: 1653-1662.
    CrossRef  |  PubMed  |  

  15. Kang, P., D. Dalvie, E. Smith and M. Renner, 2009. Bioactivation of lumiracoxib by peroxidases and human liver microsomes: identification of multiple quinone imine intermediates and GSH adducts. Chem. Res. Toxicol., 22: 106-117.
    CrossRef  |  PubMed  |  

  16. Dalvie, D., R.S. Obach, P. Kang, C. Prakash and C.M. Loi et al., 2009. Assessment of three human in vitro systems in the generation of major human excretory and circulating metabolites. Chem. Res. Toxicol., 22: 357-368.
    CrossRef  |  PubMed  |  

  17. Prakash, C., W. Chen, M. Rossulek, K. Johnson and C.H. Zhang et al., 2008. Metabolism, pharmacokinetics and excretion of a cholesteryl ester transfer protein inhibitor, torcetrapib, in rats, monkeys and mice: characterization of unusual and novel metabolites by high-resolution liquid chromatography-tandem mass spectrometry and 1H nuclear magnetic resonance. Drug Metab. Dispos., 36: 2064-2079.
    CrossRef  |  PubMed  |  

  18. Le, P.T., H. Cheng, S. Ninkovic, M. Plewe and X. Huang et al., 2008. Design and synthesis of a novel pyrrolidinyl pyrido pyrimidinone derivative as a potent inhibitor of PI3Kα and mTOR. Bioorg. Med. Chem. Lett., 22: 5098-5103.
    CrossRef  |  PubMed  |  Direct Link  |  

  19. Kang, P., D. Dalvie, E. Smith, S. Zhou, A. Deese and J.A. Nieman, 2008. Bioactivation of flutamide metabolites by human liver microsomes. Drug Metab. Dispos., 36: 1425-1437.
    CrossRef  |  PubMed  |  

  20. Dalvie, D., W. Chen, C.H. Zhang, A.D. Vaz and T.A. Smolarek et al., 2008. Pharmacokinetics, metabolism and excretion of torcetrapib, a cholesteryl ester transfer protein inhibitor, in humans. Drug Metab. Dispos., 36 : 2185-2198.
    CrossRef  |  PubMed  |  

  21. Dalvie, D., T. Cosker, T. Boyden, S. Zhou, C. Schroeder and M.J. Potchoiba, 2008. Metabolism distribution and excretion of a matrix metalloproteinase-13 inhibitor, 4-[4-(4-fluorophenoxy)-benzenesulfonylamino]tetrahydropyran-4-carboxylic acid hydroxyamide (CP-544439), in rats and dogs: assessment of the metabolic profile of CP-544439 in plasma and urine of humans. Drug Metab. Dispos., 36: 1869-1883.
    CrossRef  |  PubMed  |  

  22. Dalvie, D., P. Kang, M. Zientek, C. Xiang, S. Zhou and R.S. Obach, 2008. Effect of intestinal glucuronidation in limiting hepatic exposure and bioactivation of raloxifene in humans and rats. Chem. Res. Toxicol., 21: 2260-2271.
    CrossRef  |  PubMed  |  

  23. Zhao, S.X., D.K. Dalvie, J.M. Kelly, J.R. Soglia and K.S. Frederick et al., 2007. NADPH-Dependent covalent binding of [3H]Paroxetine to human liver microsomes and S-9 fractions: Identification of an electrophilic quinone metabolite of paroxetine. Chem. Res. Toxicol., 20: 1649-1657.
    CrossRef  |  PubMed  |  

  24. Kang, P., D. Dalvie, E. Smith, S. Zhou and A. Deese, 2007. Identification of a novel glutathione conjugate of flutamide in incubations with human liver microsomes. Drug Metab. Dispos., 35: 1081-1088.
    PubMed  |  

  25. Kalgutkar, A.S., D.K. Dalvie, J. Aubrecht, E.B. Smith and S.L. Coffing et al., 2007. Genotoxicity of 2-(3-chlorobenzyloxy)-6-(piperazinyl)pyrazine, a novel 5-hydroxytryptamine2c receptor agonist for the treatment of obesity: role of metabolic activation. Drug Metabo. Dispos., 35: 848-858.
    CrossRef  |  Direct Link  |  

  26. Bu, H.Z., P. Zhao, D. Dalvie and W.F. Pool, 2007. Identification of primary and sequential bioactivation pathways of carbamazepine in human liver microsomes using liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom., 21: 3317-3322.
    CrossRef  |  PubMed  |  

  27. Wu, M., M.R. Wester, Y.A. He, D. Dalvie and B. Holwerda et al., 2006. Site-of-metabolism prediction: A computational model based on reactivity and P450-substrate complementarity. Proceedings of the 231st ACS National Meeting, March 26-30, 2006, Atlanta, GA., USA -.

  28. Obach, R.S. and D.K. Dalvie, 2006. Metabolism of nomifensine to a dihydroisoquinolinium ion metabolite by human myeloperoxidase, hemoglobin, monoamine oxidase A and cytochrome P450 enzymes. Drug Metab. Dispos., 34: 1310-1316.
    PubMed  |  

  29. Dalvie. D., E. Smith, A. Deese and S. Bowlin, 2006. In vitro metabolic activation of thiabendazole via 5-hydroxythiabendazole: identification of a glutathione conjugate of 5-hydroxythiabendazole. Drug Metab. Dispos., 34: 709-717.
    PubMed  |  

  30. Roberts, W.G., P.M. Whalen, E. Soderstrom, G. Moraski and J.P. Lyssikatos et al., 2005. Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res., 65: 957-966.
    PubMed  |  

  31. Kalgutkar, A.S., I. Gardner, R.S. Obach, C.L. Shaffer and E. Callegari et al., 2005. A comprehensive listing of bioactivation pathways of organic functional groups. Curr. Drug Metab., 6: 161-225.
    CrossRef  |  PubMed  |  

  32. Perry, D.A., H.J. Harwood, M.R. Makowski, C.J. Coletta and J. Pyrke-Fairchild et al., 2004. Nipecotic acid derivatives as potent, nonselective acetyl-CoA carboxylase inhibitors: A novel approach for obesity. Proceedings of the 228th ACS National Meeting, August 22-26, 2004, Philadelphia, PA., USA -.

  33. Morgan, B.P., K.K.C. Liu, D.K. Dalvie, A.G. Swick and D.M. Hargrove et al., 2004. Discovery of potent, non-steroidal and highly selective glucocorticoid receptor antagonists with anti-obesity activity. Lett. Drug Des. Discovery, 1: 1-5.
    CrossRef  |  

  34. Dalvie, D.K. and T.N. O'Connell, 2004. Characterization of novel dihydrothienopyridinium and thienopyridinium metabolites of ticlopidine in vitro: Role of peroxidases, cytochromes p450 and monoamine oxidases. Drug Metab. Dispos., 32: 49-57.
    PubMed  |  

  35. O'Donnell, J.P., D.K. Dalvie, A.S. Kalgutkar and R.S. Obach, 2003. Mechanism-based inactivation of human recombinant P450 2C9 by the nonsteroidal anti-inflammatory drug suprofen. Drug Metab. Dispos., 31: 1369-1377.
    PubMed  |  

  36. Kalgutkar, A.S., H.T. Nguyen, A.D. Vaz, A. Doan, D.K. Dalvie, D.G. McLeod and J.C. Murray, 2003. In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent leflunomide to its active &alpha-cyanoenol metabolite A771726: Mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes. Drug Metab. Dispos., 31: 1240-1250.
    PubMed  |  

  37. Harwood Jr., H.J., S.F. Petras, L.D. Shelly, L.M. Zaccaro and D.A. Perry et al., 2003. Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis and increase fatty acid oxidation in cultured cells and in experimental animals. J. Biol. Chem., 278: 37099-37111.
    PubMed  |  

  38. Kalgutkar, A.S., D.K. Dalvie, J.P. O'Donnell, T.J. Taylor and D.C. Sahakian, 2002. On the diversity of oxidative bioactivation reactions on nitrogen-containing xenobiotics. Curr. Drug Metab., 3: 379-424.
    PubMed  |  

  39. Dalvie, D.K., A.S. Kalgutkar, S.C. Khojasteh-Bakht, R.S. Obach and J.P. O'Donnell, 2002. Biotransformation reactions of five-membered aromatic heterocyclic rings. Chem. Res. Toxicol., 15: 269-299.
    PubMed  |  

  40. Liu, K.K.C., B.P. Morgan, R.L. Dow, P.A. McCarthy and P. Silva-Jardine et al., 2001. Novel, selective non-steroidal glucocorticoid receptor modulators (SGRM's) for the treatment of obesity. Proceedings of the 222nd ACS National Meeting, August 26-30, 2001, Chicago, IL., USA -.

  41. Kalgutkar, A.S., D.K. Dalvie, N. Castagnoli Jr. and T.J. Taylor, 2001. Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrates and inhibitors. Chem. Res. Toxicol., 14: 1139-1162.
    PubMed  |  

  42. Dalvie, D., 2000. Applications of radiolabelled compounds in pharmacokinetics, toxicology and metabolism. Curr. Pharm. Des., 6: 1009-1028.

  43. Dalvie, D.K. and J.P. O'Donnell, 1999. Metabolism of CP-195,543, a leukotriene B4 receptor antagonist, in the long-evans rat and cynomolgus monkey. Xenobiotica, 29: 1123-1140.
    PubMed  |  

  44. Dalvie, D.K. and J. O'Donnell, 1999. Metabolism of pamaqueside, a cholesterol absorption inhibitor, in Long-Evans rat: effect of bile duct cannulation on absorption. Xenobiotica, 29: 1043-1056.
    PubMed  |  

  45. Vincent, J., R. Teng, D.K. Dalvie and H.L. Friedman, 1998. Pharmacokinetics and metabolism of single oral doses of trovafloxacin. Am. J. Surg., 76: 8S-13S.
    PubMed  |  

  46. O'Donnell, J.P., N.B. Khosla and D.K. Dalvie, 1998. Metabolism of droloxifene in the CD-1 mouse, Fischer-344 rat and Cynomolgus monkey. Xenobiotica, 28: 153-166.
    PubMed  |  

  47. Dalvie, D.K. and J.P. O'Donnell, 1998. Characterization of polar urinary metabolites by ionspray tandem mass spectrometry following dansylation. Rapid Commun. Mass Spectrom., 12: 419-422.
    CrossRef  |  PubMed  |  Direct Link  |  

  48. Dalvie, D. and J.P. O'Donnell, 1998. Metabolism of CP-195,543 in rat and monkey. Proceedings of the 5th International ISSX Meeting, October 25 - 29, 1998, Cairns, Australia. -.

  49. Ramakrishna, K.V., P.W. Fan, C.S. Boyer, D. Dalvie and J.L. Bolton, 1997. Oxo substituents markedly alter the phase II metabolism of α-hydroxybutenylbenzenes: Models probing the bioactivation mechanisms of tamoxifen. Chem. Res. Toxicol., 10: 887-894.
    CrossRef  |  PubMed  |  Direct Link  |  

  50. Fouda, H.G., M.J. Avery, D. Dalvie, F.C. Falkner, L.S. Melvin and R.A. Ronfeld, 1997. Disposition and metabolism of tenidap in the rat. Drug Metab. Dispos., 25: 140-148.
    PubMed  |  

  51. Dalvie, D.K., N.B. Khosla and J. Vincent, 1997. Excretion and metabolism of trovafloxacin in humans. Drug Metab. Dispos., 25: 423-427.
    PubMed  |  

  52. Dalvie, D. and J. O'Donnell, 1997. HPLC/ESI/MS/MS characterization of metabolites following chemical derivatization. Proceedings of the 27th Gordon Research Conference on Drug Metabolism, July, 1997, Plymouth, UK -.

  53. Dalvie, D., N. Khosla, K.A. Navetta and K.E. Brighty, 1996. Metabolism and excretion of trovafloxacin, a new quinolone antibiotic, in Sprague-Dawley rats and beagle dogs. Effect of bile duct cannulation on excretion pathways. Drug Metab. Dispos., 24: 1231-1240.
    PubMed  |  

  54. Dalvie, D., J. O'Donnell and N. Khosla, 1996. Metabolism of droloxifene in mouse, rat and monkey. Proceedings of the 7th North American ISSX Meeting, October, 1996, San Diego, CA., USA -.

  55. Dalvie, D., N. Khosla and J. Vincent, 1995. Metabolism of a new quinolone antibiotic, CP-99,219 in humans. Proceedings of the 4th International ISSX Meeting, August, 1995, Seattle, WA., USA -.

  56. Dalvie, D., N. Khosla and J. O'Donnell, 1995. Metabolism of CP-148,623, a new cholesterol absorption inhibitor, in Long-Evans rats. Proceedings of the 4th International ISSX Meeting, August, 1995, Seattle, WA., USA -.

  57. Dalvie, D. and J. O'Donnell, 1995. Metabolism of CP-148,623, a new cholesterol absorption inhibitor, in Beagle dogs. Proceedings of the 4th International ISSX Meeting, August, 1995, Seattle, WA., USA -.

  58. Fouda, H.G., M.J. Avery, D.K. Dalvie, F.C. Falkner, K.A. Navetta, L. Melvin and F. Rusek, 1994. Metabolism of the antiinflamatory tenidap, in the rat. Identification of biliary metabolites by atmospheric pressure ionization mass spectrometry. Proceedings of the 42nd ASMS Conference on Mass Spectrometry, May 29-June 3, 1994, Chicago, USA -.

  59. Dalvie, D., K.A. Navetta and N. Khosla, 1994. Excretion and metabolism of a new quinolone antibiotic, CP99,219, in Sprague-Dawley rats and beagle dogs. Proceedings of the 6th North American ISSX Meeting, October, 1994, Raleigh, NC., USA -.

  60. Avery, M.J., K.A. Navetta, D.K. Dalvie, F.C. Falkner and H.G. Fouda, 1994. Identification of tenidap metabolites in monkey by HPLC/Atmospheric pressure ionization mass spectrometry and simultaneous radioactivity monitoring. Proceedings of the 42nd ASMS Conference on Mass Spectrometry, May 29-June 3, 1994, Chicago, USA -.

  61. Sundberg, R.J., D.K. Dalvie, J. Cordero and H.A. Musallam, 1993. Carbamate derivatives of 2-arylimidazo[1,2-a]pyridinium salts as acetylcholinesterase inhibitors and protective agents against organophosphorus compounds. Chem. Res. Toxicol., 6: 506-510.
    PubMed  |  

  62. Sundberg, R.J., D. Dalvie, J. Cordero, M. Sabat and H.A. Musallam, 1993. Carbamates of (Hydroxyphenoxy)methyl heteroaromatic salts as acetylcholinesterase inhibitors and protective agents against organophosphorus compounds. Chem. Res. Toxicol 6: 500-505.
    PubMed  |  

  63. Anderson, W.K. and D.K. Dalvie, 1993. Synthesis of 4-(2-chloroethyl)-2,3-dihydro[1,4]oxazino[2,3-b]quinoline and 4-(2-chloroethyl)2,3-dihydropyrido[2,3-b][1,4]oxazine. J. Heterocyclic Chem., 30: 1533-1536.
    CrossRef  |  Direct Link  |  

  64. Zhao, Z., D. Dalvie, N. Naiman, K. Castagnoli and N. Castagnoli Jr., 1992. Design, synthesis and biological evaluation of novel 4-substituted 1-methyl-1,2,3,6-tetrahydropyridine analogs of MPTP. J. Med. Chem., 35: 4473-4478.
    PubMed  |  

  65. Dalvie, D., Z. Zhao and N. Castagnoli Jr., 1992. Synthetic and metabolic studies of 4-acyloxytetrahydropyridines. Proceedings of the Meeting of American Chemical Society, August, 1992, Washington DC., USA -.

  66. Dalvie, D., Z. Zhao and N. Castagnoli Jr., 1992. Characterization of an unexpected product from a monoamine oxidase B generated 2,3-dihydropyridinium species. J. Org. Chem., 57: 7321-7324.
    CrossRef  |  

  67. Dalvie, D., R.J. Sundberg and J. Cordero, 1991. Imidazolium, pyridinium and imidazo[1,2-α]pyridinium salts as reversible inhibitors of acetylcholinesterase. Proceedings of the Meeting of American Chemical Society, August, 1991, Atlanta, GA., USA -.