Читать книгу Successful Drug Discovery, Volume 5 - Группа авторов - Страница 36

1 1 Iervolino, A. and Urquhart, L. (ed.) (2017). EvaluatePharma World Preview 2017, Outlook to 2022, 10th ed, 19.

2 2 Philippidis, A. (2019). Genetic Engineering & Biotechnology News, vol. 2020. Mary Ann Liebert, Inc. Publishers.

3 3 Mullard, A. (2020). 2019 FDA drug approvals. Nat. Rev. Drug Discovery 19: 79–84.

4 4 Stevens, A.J., Jensen, J.J., Wyller, K. et al. (2011). The role of public‐sector research in the discovery of drugs and vaccines. N. Engl. J. Med. 364: 535–541.

5 5 Nayak, R.K., Avorn, J., and Kesselheim, A.S. (2019). Public sector financial support for late stage discovery of new drugs in the United States: cohort study. BMJ 367: l5766.

6 6 Edwards, J.C.W., Cambridge, G., and Abrahams, V.M. (1999). Do self‐perpetuating B lymphocytes drive human autoimmune disease? Immunology 97: 188–196.

7 7 Protheroe, A., Edwards, J.C.W., Simmons, A. et al. (1999). Remission of inflammatory arthropathy in association with anti‐CD20 therapy for non‐Hodgkin's lymphoma. Rheumatology 38: 1150–1152.

8 8 Edwards, J.C.W., Szczepanski, L., Szechinski, J. et al. (2004). Efficacy of B‐cell‐targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350: 2572–2581.

9 9 (a) Sheskin, J. (1965). Thalidomide in the treatment of lepra reactions. Clin. Pharmacol. Ther. 6: 303–306.(b) Sheskin, J. (1980). The treatment of lepra reaction in lepromatous leprosy – 15 years experience with thalidomide. Int. J. Dermatol. 19: 318–322.

10 10 D'Amato, R.J., Loughnan, M.S., Flynn, E., and Folkman, J. (1994). Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. U. S. A. 91: 4082–4085.

11 11 Singhal, S., Mehta, J., Desikan, R. et al. (1999). Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 341: 1565–1571.

12 12 Olson, K.B., Hall, T.C., Horton, J. et al. (1965). Thalidomide (N‐phthaloylglutamimide) in treatment of advanced cancer. Clin. Pharmacol. Ther. 6: 292.

13 13 Krumbhaar, E.B. and Krumbhaar, H.D. (1919). The blood and bone marrow in yelloe cross gas (mustard gas) poisoning: changes produced in the bone marrow of fatal cases. J. Med. Res. 40: 497–508. 493.

14 14 Gilman, A. and Philips, F.S. (1946). The biological actions and therapeutic applications of the B‐chloroethyl amines and sulfides. Science 103: 409–415.

15 15 Fenn, J.E. and Udelsman, R. (2011). First use of intravenous chemotherapy cancer treatment: rectifying the record. J. Am. Coll. Surgeons 212: 413–417.

16 16 Goodman, L.S., Wintrobe, M.M. et al. (1946). Nitrogen mustard therapy; use of methyl‐bis (beta‐chloroethyl) amine hydrochloride and tris (beta‐chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J. Am. Med. Assoc. 132: 126–132.

17 17 (a) DeVita, V.T. Jr. and Chu, E. (2008). A history of cancer chemotherapy. Cancer Res. 68: 8643–8653.(b) Verrill, M. (2009). Chemotherapy for early‐stage breast cancer: a brief history. Br. J. Cancer 101 (Suppl 1): S2–S5.(c) Galmarini, D., Galmarini, C.M., and Galmarini, F.C. (2012). Cancer chemotherapy: a critical analysis of its 60 years of history. Crit. Rev. Oncol. Hematol. 84: 181–199.

18 18 (a) Silverman, R.B. (2016). Basic science to blockbuster drug: invention of Pregabalin (Lyrica (R)). Technol. Innov. 17: 153–158.(b) Silverman, R.B. (2008). From basic science to blockbuster drug: the discovery of Lyrica. Angew. Chem. Int. Ed. 47: 3500–3504.

19 19 Krnjevic, K. (1970). Glutamate and gamma‐aminobutyric acid in brain. Nature 228: 119.

20 20 Baxter, C.F. and Roberts, E. (1961). Elevation of gamma‐aminobutyric acid in brain – selective inhibition of gamma‐aminobutyric‐alpha‐ketoglutaric acid transaminase. J. Biolumin. Chemilumin. 236: 3287.

21 21 Kuriyama, K., Roberts, E., and Rubinstein, M.K. (1966). Elevation of gamma‐aminobutyric acid in brain with amino‐oxyacetic acid and susceptibility to convulsive seizures in mice: a quantitative re‐evaluation. Biochem. Pharmacol. 15: 221–236.

22 22 Loscher, W. (1980). A comparative study of the pharmacology of inhibitors of GABA‐metabolism. Naunyn‐Schmiedeberg's Arch. Pharmacol. 315: 119–128.

23 23 Silverman, R.B. and Levy, M.A. (1980). Irreversible inactivation of pig brain gamma‐aminobutyric acid‐alpha‐ketoglutarate transaminase by 4‐amino‐5‐halopentanoic acids. Biochem. Bioph. Res. Co. 95: 250–255.

24 24 (a) Taylor, C.P., Vartanian, M.G., Andruszkiewicz, R., and Silverman, R.B. (1992). 3‐Alkyl GABA and 3‐alkylglutamic acid analogs – 2 new classes of anticonvulsant agents. Epilepsy Res. 11: 103–110.(b) Silverman, R.B., Andruszkiewicz, R., Nanavati, S.M. et al. (1991). 3‐Alkyl‐4‐aminobutyric acids – the 1st class of anticonvulsant agents that activates l‐glutamic acid decarboxylase. J. Med. Chem. 34: 2295–2298.

25 25 Verrey, F. (2003). System L: heteromeric exchangers of large, neutral amino acids involved in directional transport. Pflug. Arch. Eur. J. Phy. 445: 529–533.

26 26 Patridge, E., Gareiss, P., Kinch, M.S., and Hoyer, D. (2016). An analysis of FDA‐approved drugs: natural products and their derivatives. Drug Discovery Today 21: 204–207.

27 27 Fleming, A. (1929). On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ. Br. J. Exp. Pathol. 10: 226–236.

28 28 Gaynes, R. (2017). The discovery of penicillin – new insights after more than 75 years of clinical use. Emerg. Infect. Dis. 23: 849–853.

29 29 Tan, S. and Tatsumura, Y. (2015). Alexander Fleming (1881–1955): discoverer of penicillin. Singapore Med. J. 56: 366–367.

30 30 Schatz, A., Bugie, E., and Waksman, S.A. (1944). Streptomycin, a substance exhibiting antibiotic activity against gram‐positive and gram‐negative bacteria. Clin. Orthop. Relat. Res. 2005: 3–6.

31 31 (a) Pringle, P. and Moss, D.W. (2012). Experiment eleven: deceit and betrayal in the discovery of the cure for tuberculosis. London; New York: Bloomsbury.(b) Wainwright, M. (1991). Streptomycin – discovery and resultant controversy. Hist. Phil. Life Sci. 13: 97–124.

32 32 Gall, Y.M. and Konashev, M.B. (2001). The discovery of Gramicidin S: the intellectual transformation of G.F. Gause from biologist to researcher of antibiotics and on its meaning for the fate of Russian genetics. Hist. Phil. Life Sci. 23: 137–150.

33 33 Zubrod, C.G., Schepartz, S.A., and Carter, S.K. (1977). Historical background of the National Cancer Institute's drug development thrust. Natl. Cancer Inst. Monogr.: 7–11.

34 34 Wall, M.E., Wani, M.C., Cook, C.E. et al. (1966). Plant antitumor agents. I. Isolation and structure of camptothecin a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J. Am. Chem. Soc. 88: 3888–3890.

35 35 Stork, G. and Schultz, A.G. (1971). The total synthesis of dl‐camptothecin. J. Am. Chem. Soc. 93: 4074–4075.

36 36 (a) Danishefsky, S., Etheredge, S.J., Volkmann, R. et al. (1971). Nucleophilic additions to allenes – New synthesis of alpha‐pyridones. J. Am. Chem. Soc. 93: 5575.(b) Volkmann, R., Danishefsky, S., Eggler, J., and Solomon, D.M. (1971). Total synthesis of dl‐camptothecin. J. Am. Chem. Soc. 93: 5576.

37 37 Boch, M., Winterfeldt, E., Nelke, J.M. et al. (1972). Reactions with indole‐derivatives. 17. Biogenetically orientated total‐synthesis of dl‐camptothecin and 7‐chlorocamptothecin. Chem. Ber‐Recl. 105: 2126.

38 38 (a) Hertzberg, R.P., Caranfa, M.J., and Hecht, S.M. (1989). On the mechanism of topoisomerase‐I inhibition by camptothecin – evidence for binding to an enzyme DNA complex. Biochemistry 28: 4629–4638.(b) Staker, B.L., Feese, M.D., Cushman, M. et al. (2005). Structures of three classes of anticancer agents bound to the human topoisomerase I − DNA covalent complex. J. Med. Chem. 48: 2336–2345.

39 39 Wani, M.C., Taylor, H.L., Wall, M.E. et al. (1971). Plant antitumor agents. 6. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus‐Brevifolia. J. Am. Chem. Soc. 93: 2325.

40 40 Wilson, C.R., Sauer, J.‐M., and Hooser, S.B. (2001). Taxines: a review of the mechanism and toxicity of yew (Taxus spp.) alkaloids. Toxicon 39: 175–185.

41 41 Horwitz, S.B. (2019). Reflections on my life with taxol. Cell 177: 502–505.

42 42 (a) Schiff, P.B., Fant, J., and Horwitz, S.B. (1979). Promotion of microtubule assembly invitro by taxol. Nature 277: 665–667.(b) Schiff, P.B. and Horwitz, S.B. (1980). Taxol stabilizes microtubules in mouse fibroblast cells. Proc. Natl. Acad. Sci. U. S. A. 77: 1561–1565.

43 43 (a) Holton, R.A., Somoza, C., Kim, H.B. et al. (1994). First total synthesis of taxol. 1. Functionalization of the B‐ring. J. Am. Chem. Soc. 116: 1597–1598.(b) Holton, R.A., Kim, H.B., Somoza, C. et al. (1994). First total synthesis of taxol. 2. Completion of the C‐ring and D‐ring. J. Am. Chem. Soc. 116: 1599–1600.

44 44 Nicolaou, K.C., Yang, Z., Liu, J.J. et al. (1994). Total synthesis of taxol. Nature 367: 630–634.

45 45 Masters, J.J., Link, J.T., Snyder, L.B. et al. (1995). A total synthesis of taxol. Angew. Chem. Int. Ed. 34: 1723–1726.

46 46 Wender, P.A. and Mucciaro, T.P. (1992). A new and practical approach to the synthesis of taxol and taxol analogs – the pinene path. J. Am. Chem. Soc. 114: 5878–5879.

47 47 (a) Morihira, K., Hara, R., Kawahara, S. et al. (1998). Enantioselective total synthesis of taxol. J. Am. Chem. Soc. 120: 12980–12981.(b) Kusama, H., Hara, R., Kawahara, S. et al. (2000). Enantioselective total synthesis of (‐)‐taxol. J. Am. Chem. Soc. 122: 3811–3820.

48 48 Mukaiyama, T., Shiina, I., Iwadare, H. et al. (1999). Asymmetric total synthesis of Taxol (R). Chem‐Eur. J. 5: 121–161.

49 49 Takahashi, T., Okabe, T., Iwamoto, H. et al. (1997). A biomimetic approach to taxol: stereoselective synthesis of a 12‐membered ring ene‐epoxide. Isr. J. Chem. 37: 31–37.

50 50 McGuire, W.P., Rowinsky, E.K., Rosenshein, N.B. et al. (1989). Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann. Intern. Med. 111: 273–279.

51 51 Gore, A. (2006). An Inconvenient Truth: the Planetary Emergency of Global Warming and What We Can Do About It. London: Bloomsbury.

52 52 Walsh, V. and Goodman, J. (1999). Cancer chemotherapy, biodiversity, public and private property: the case of the anti‐cancer drug Taxol. Soc. Sci. Med. 49: 1215–1225.

53 53 Denis, J.N., Greene, A.E., Guenard, D. et al. (1988). A highly efficient, practical approach to natural taxol. J. Am. Chem. Soc. 110: 5917–5919.

54 54 Singla, A.K., Garg, A., and Aggarwal, D. (2002). Paclitaxel and its formulations. Int. J. Pharm. 235: 179–192.

55 55 Hirsh, V. (2014). nab‐paclitaxel for the management of patients with advanced non‐small‐cell lung cancer. Expert Rev. Anticancer Ther. 14: 129–141.

56 56 Hofle, G.H., Bedorf, N., Steinmetz, H. et al. (1996). Epothilone A and B – novel 16‐membered macrolides with cytotoxic activity: isolation, crystal structure, and conformation in solution. Angew. Chem. Int. Ed. 35: 1567–1569.

57 57 (a) Su, D.‐S., Meng, D., Bertinato, P. et al. (1997). Total synthesis of(–)‐epothilone B: an extension of the Suzuki coupling method and insights into structure–activity relationships of the epothilones. Angew. Chem. Int. Ed. 36: 757–759.(b) Balog, A., Meng, D.F., Kamenecka, T. et al. (1996). Total synthesis of (−)‐epothilone A. Angew. Chem. Int. Ed. 35: 2801–2803.

58 58 (a) Yang, Z., He, Y., Vourloumis, D. et al. (1997). Total synthesis of epothilone A: the olefin metathesis approach. Angew. Chem. Int. Ed. 36: 166–168.(b) Nicolaou, K.C., Ninkovic, S., Sarabia, F. et al. (1997). Total syntheses of epothilones A and B via a macrolactonization‐based strategy. J. Am. Chem. Soc. 119: 7974–7991.

59 59 (a) Furstner, A., Mathes, C., and Grela, K. (2001). Concise total syntheses of epothilone A and C based on alkyne metathesis. Chem. Commun.: 1057–1059.(b) Furstner, A., Mathes, C., and Lehmann, C.W. (2001). Alkyne metathesis: development of a novel molybdenum‐based catalyst system and its application to the total synthesis of epothilone A and C. Chem‐Eur. J. 7: 5299–5317.

60 60 Schinzer, D., Limberg, A., Bauer, A. et al. (1997). Total synthesis of (−)‐epothilone A. Angew. Chem. Int. Ed. 36: 523–524.

61 61 Bode, J.W. and Carreira, E.M. (2001). Stereoselective syntheses of epothilones A and B via directed nitrile oxide cycloaddition1. J. Am. Chem. Soc. 123: 3611–3612.

62 62 Mulzer, J., Mantoulidis, A., and Öhler, E. (2000). Total syntheses of epothilones B and D. J. Org. Chem. 65: 7456–7467.

63 63 Lee, F.Y.F., Borzilleri, R., Fairchild, C.R. et al. (2008). Preclinical discovery of ixabepilone, a highly active antineoplastic agent. Cancer Chemother. Pharmacol. 63: 157–166.

64 64 (a) Hirata, Y. and Uemura, D. (1986). Halichondrins – antitumor polyether macrolides from a marine sponge. Pure Appl. Chem. 58: 701–710.(b) Uemura, D., Takahashi, K., Yamamoto, T. et al. (1985). Norhalichondrin‐A – an antitumor polyether macrolide from a marine sponge. J. Am. Chem. Soc. 107: 4796–4798.

65 65 Hart, J.B., Lill, R.E., Hickford, S.J.H. et al. (2000). The halichondrins: chemistry, biology, supply and delivery. In: Drugs from the Sea (ed. N. Fusetani), 134–153. Basel: Karger.

66 66 Aicher, T.D., Buszek, K.R., Fang, F.G. et al. (1992). Total synthesis of halichondrin‐B and norhalichondrin‐B. J. Am. Chem. Soc. 114: 3162–3164.

67 67 (a) Bauer, A. (2016). Synthesis of Heterocycles in Contemporary Medicinal Chemistry (ed. Z. Časar), 209–270. Cham: Springer International Publishing.(b) Jackson, K.L., Henderson, J.A., and Phillips, A.J. (2009). The halichondrins and E7389. Chem. Rev. 109: 3044–3079.

68 68 (a) Cortes, J., O'Shaughnessy, J., Loesch, D. et al. (2011). Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open‐label randomised study. Lancet 377: 914–923.(b) Cortes, J., Twelves, C., Wanders, J. et al. (2011). Clinical response to eribulin in patients with metastatic breast cancer is independent of time to first metastatic event. EMBRACE study group. Breast 20: S48–S49.

69 69 (a) Kim, D.S., Dong, C.G., Kim, J.T. et al. (2009). New syntheses of E7389 C14‐C35 and halichondrin C14‐C38 building blocks: double‐inversion approach. J. Am. Chem. Soc. 131: 15636–15641.(b) Dong, C.G., Henderson, J.A., Kaburagi, Y. et al. (2009). New syntheses of E7389 C14‐C35 and halichondrin C14‐C38 building blocks: reductive cyclization and oxy‐Michael cyclization approaches. J. Am. Chem. Soc. 131: 15642–15646.(c) Yang, Y.R., Kim, D.S., and Kishi, Y. (2009). Second generation synthesis of C27‐C35 building block of E7389, a synthetic halichondrin analogue. Org. Lett. 11: 4516–4519.

70 70 (a) Yu, M.J., Zheng, W.J., and Seletsky, B.M. (2013). From micrograms to grams: scale‐up synthesis of eribulin mesylate. Nat. Prod. Rep. 30: 1158–1164.(b) Austad, B.C., Calkins, T.L., Chase, C.E. et al. (2013). Commercial manufacture of Halaven (R): chemoselective transformations en route to structurally complex macrocyclic ketones (vol 24, pg 333, 2013). Synlett 24, E3‐E3.(c) Fukuyama, T., Chiba, H., Kuroda, H. et al. (2016). Application of continuous flow for DIBAL‐H reduction and n‐BuLi mediated coupling reaction in the synthesis of eribulin mesylate. Org. Process Res. Dev. 20: 503–509.(d) Fukuyama, T., Chiba, H., Takigawa, T. et al. (2016). Application of a rotor stator high‐shear system for Cr/Mn‐mediated reactions in eribulin mesylate synthesis. Org. Process Res. Dev. 20: 100–104.

71 71 Kawano, S., Ito, K., Yahata, K. et al. (2019). A landmark in drug discovery based on complex natural product synthesis. Sci. Rep. 9: 8656.

72 72 Levesque, F. and Seeberger, P.H. (2012). Continuous‐flow synthesis of the anti‐malaria drug artemisinin. Angew. Chem. Int. Ed. 51: 1706–1709.

73 73 (a) Chang, Z.Y. (2016). The discovery of Qinghaosu (artemisinin) as an effective anti‐malaria drug: a unique China story. Sci. China Life Sci. 59: 81–88.(b) Tu, Y.Y. (2011). The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat. Med. 17: 1217–1220.(c) Wang, M.Y. (2016). Publication process involving the discovery of artemisinin (qinghaosu) before 1985. Asian Pac. J. Trop. Biomed. 6: 461–467.(d) Jianfang, Z. and Arnold, K.M. (2013). A Detailed Chronological Record of Project 523 and the Discovery and Development of Qinghaosu (Artemisinin). Strategic Book Publishing and Rights Company.

74 74 Gilmore, K., Kopetzki, D., Lee, J.W. et al. (2014). Continuous synthesis of artemisinin‐derived medicines. Chem. Commun. 50: 12652–12655.

75 75 Turconi, J., Griolet, F., Guevel, R. et al. (2014). Semisynthetic artemisinin, the chemical path to industrial production. Org. Process Res. Dev. 18: 417–422.

76 76 Hanada, M., Sugawara, K., Kaneta, K. et al. (1992). Epoxomicin, a new antitumor agent of microbial origin. J. Antibiot. 45: 1746–1752.

77 77 Sin, N., Kim, K.B., Elofsson, M. et al. (1999). Total synthesis of the potent proteasome inhibitor epoxomicin: a useful tool for understanding proteasome biology. Bioorg. Med. Chem. Lett. 9: 2283–2288.

78 78 Meng, L., Mohan, R., Kwok, B.H.B. et al. (1999). Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc. Natl. Acad. Sci. U. S. A. 96: 10403–10408.

79 79 Myung, J., Kim, K.B., and Crews, C.M. (2001). The ubiquitin‐proteasome pathway and proteasome inhibitors. Med. Res. Rev. 21: 245–273.

80 80 Groll, M., Kim, K.B., Kairies, N. et al. (2000). Crystal structure of epoxomicin: 20S proteasome reveals a molecular basis for selectivity of alpha',beta'‐epoxyketone proteasome inhibitors. J. Am. Chem. Soc. 122: 1237–1238.

81 81 Elofsson, M., Splittgerber, U., Myung, J. et al. (1999). Towards subunit‐specific proteasome inhibitors: synthesis and evaluation of peptide α',β'‐epoxyketones. Chem. Biol. 6: 811–822.

82 82 Rosenfeld, L. (2002). Insulin: discovery and controversy. Clin. Chem. 48: 2270–2288.

83 83 Beals, J.M. (2005). Successful Drug Discovery, vol. 1, 35–60. Weinheim: Wiley‐VCH.

84 84 Banting, F.G., Best, C.H., Collip, J.B. et al. (1922). Pancreatic extracts in the treatment of diabetes mellitus. Can. Med. Assoc. J. 12: 141–146.

85 85 Zuelzer, G. (1908). Ueber Versuche einer specifischen Fermenttherapie des Diabetes. Zeitschrift f. exp. Pathologie u. Therapie 5: 307–318.

86 86 Scott, E.L. (1912). On the influence of intravenous injections of an extract of the pancreas on experimental pancreatic diabetes. Am. J. Physiol. 29: 306–310.

87 87 Ionescu‐Tirgoviste, C. and Buda, O. (2017). Nicolae Constantin Paulescu. The First Explicit Description of the Internal Secretion of the Pancreas. Acta Med. Hist. Adriat. 15: 303–322.

88 88 Kohler, G. and Milstein, C. (1975). Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256: 495–497.

89 89 Stashenko, P., Nadler, L.M., Hardy, R., and Schlossman, S.F. (1980). Characterization of a human B lymphocyte‐specific antigen. J. Immunol. 125: 1678–1685.

90 90 Tedder, T.F., Streuli, M., Schlossman, S.F., and Saito, H. (1988). Isolation and structure of a cDNA encoding the B1 (CD20) cell‐surface antigen of human B lymphocytes. Proc. Natl. Acad. Sci. U. S. A. 85: 208–212.

91 91 Nadler, L.M., Stashenko, P., Hardy, R. et al. (1980). Serotherapy of a patient with a monoclonal‐antibody directed against a human lymphoma‐associated antigen. Cancer Res. 40: 3147–3154.

92 92 (a) Boulianne, G.L., Hozumi, N., and Shulman, M.J. (1984). Production of functional chimaeric mouse/human antibody. Nature 312: 643–646.(b) Morrison, S.L., Johnson, M.J., Herzenberg, L.A., and Oi, V.T. (1984). Chimeric human antibody molecules: mouse antigen‐binding domains with human constant region domains. Proc. Natl. Acad. Sci. U. S. A. 81: 6851–6855.

93 93 (a) Lampson, L.A. and Levy, R. (1979). A role for clonal antigens in cancer diagnosis and therapy. J. Natl. Cancer Inst. 62: 217–220.(b) Levy, R., Warnke, R., Dorfman, R.F., and Haimovich, J. (1977). The monoclonality of human B‐cell lymphomas. J. Exp. Med. 145: 1014–1028.

94 94 Miller, R.A., Maloney, D.G., Warnke, R., and Levy, R. (1982). Treatment of B‐cell lymphoma with monoclonal anti‐idiotype antibody. N. Engl. J. Med. 306: 517–522.

95 95 Pierpont, T.M., Limper, C.B., and Richards, K.L. (2018). Past, present, and future of rituximab – the world's first oncology monoclonal antibody therapy. Front. Oncol. 8: 163.

96 96 Maloney, D.G., Liles, T.M., Czerwinski, D.K. et al. (1994). Phase‐I clinical‐trial using escalating single‐dose infusion of chimeric anti‐Cd20 monoclonal‐antibody (Idec‐C2b8) in patients with recurrent B‐cell lymphoma. Blood 84: 2457–2466.

97 97 Brady, R.O., Kanfer, J.N., Bradley, R.M., and Shapiro, D. (1966). Demonstration of a deficiency of glucocerebroside‐cleaving enzyme in Gaucher's disease. J. Clin. Invest. 45: 1112–1115.

98 98 Brady, R.O., Pentchev, P.G., Gal, A.E. et al. (1974). Replacement therapy for inherited enzyme deficiency – use of purified glucocerebrosidase in Gauchers‐disease. New Engl. J. Med. 291: 989–993.

99 99 Brady, R.O. and Barton, N.W. (1994). Enzyme replacement therapy for Gaucher disease – critical investigations beyond demonstration of clinical efficacy. Biochem. Med. Metab. B 52: 1–9.

100 100 Brady, R.O. and Barton, N.W. (1996). Enzyme replacement and gene therapy for Gaucher's disease. Lipids 31: S137–S139.

101 101 Deegan, P.B. and Cox, T.M. (2012). Imiglucerase in the treatment of Gaucher disease: a history and perspective. Drug Des. Dev. Ther. 6: 81.

102 102 Breslow, R. (2016). Successful Drug Discovery, vol. 2 (ed. W.E.C. János Fischer), 1–11. Weinheim: Wiley‐VCH.

103 103 Yoshida, M., Kijima, M., Akita, M., and Beppu, T. (1990). Potent and specific‐inhibition of mammalian histone deacetylase both invivo and invitro by trichostatin‐A. J. Biolumin. Chemilumin. 265: 17174–17179.

104 104 Finnin, M.S., Donigian, J.R., Cohen, A. et al. (1999). Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 401: 188–193.

105 105 Kelly, W.K., Richon, V.M., O'Connor, O. et al. (2003). Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin. Cancer Res. 9: 3578–3588.

106 106 Molina, A.M., Van Der Mijn, J.C., Christos, P. et al. (2020). NCI 6896: a phase I trial of vorinostat (SAHA) and isotretinoin (13‐cis retinoic acid) in the treatment of patients with advanced renal cell carcinoma. Invest. New Drugs.

107 107 Schiedel, M. and Conway, S.J. (2018). Small molecules as tools to study the chemical epigenetics of lysine acetylation. Curr. Opin. Chem. Biol. 45: 166–178.

108 108 (a) Eckschlager, T., Plch, J., Stiborova, M., and Hrabeta, J. (2017). Histone deacetylase inhibitors as anticancer drugs. Int. J. Mol. Sci. 18: 1414.(b) Jiang, Z.F., Li, W., Hu, X.C. et al. (2019). Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor‐positive breast cancer (ACE): a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet Oncol. 20: 806–815.(c) Yang, F., Zhao, N., Hu, Y. et al. (2020). The development process: from SAHA to hydroxamate HDAC inhibitors with branched CAP region and linear linker. Chem. Biodivers. 17: e1900427.(d) Zhang, Q., Wang, S., Chen, J., and Yu, Z. (2019). Histone deacetylases (HDACs) guided novel therapies for T‐cell lymphomas. Int. J. Med. Sci. 16: 424–442.

109 109 Lu, X.P., Ning, Z.‐Q., Li, Z.‐B. et al. (2016). Successful Drug Discovery (ed. W.E.C.J. Fischer), 89–114. Weinheim: Wiley‐VCH.

110 110 Prusoff, W.H. (1959). Synthesis and biological activities of iododeoxyuridine, an analog of thymidine. Biochim. Biophys. Acta 32: 295–296.

111 111 Clercq, E.D. and Holý, A. (2005). Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nat. Rev. Drug Discovery 4: 928–940.

112 112 De Clercq, E., Descamps, J., De Somer, P., and Holy, A. (1978). (S)‐9‐(2,3‐Dihydroxypropyl)adenine: an aliphatic nucleoside analog with broad‐spectrum antiviral activity. Science 200: 563–565.

113 113 Declercq, E., Holy, A., Rosenberg, I. et al. (1986). A novel selective broad‐spectrum anti‐DNA virus agent. Nature 323: 464–467.

114 114 De Clercq, E., Sakuma, T., Baba, M. et al. (1987). Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res. 8: 261–272.

115 115 Pradere, U., Garnier‐Amblard, E.C., Coats, S.J. et al. (2014). Synthesis of nucleoside phosphate and phosphonate prodrugs. Chem. Rev. 114: 9154–9218.

116 116 Wittayanarakul, K., Aruksakunwong, O., Saen‐Oon, S. et al. (2005). Insights into saquinavir resistance in the G48V HIV‐1 protease: quantum calculations and molecular dynamic simulations. Biophys. J. 88: 867–879.

117 117 Ghosh, A.K., Sridhar, P.R., Leshchenko, S. et al. (2006). Structure‐based design of novel HIV‐1 protease inhibitors to combat drug resistance. J. Med. Chem. 49: 5252–5261.

118 118 (a) Ghosh, A.K., Anderson, D.D., Weber, I.T., and Mitsuya, H. (2012). Enhancing protein backbone binding – a fruitful concept for combating drug‐resistant HIV. Angew. Chem. Int. Ed. 51: 1778–1802.(b) Ghosh, A.K., Chapsal, B.D., Weber, I.T., and Mitsuya, H. (2008). Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. Acc. Chem. Res. 41: 78–86.

119 119 Surleraux, D.L., Tahri, A., Verschueren, W.G. et al. (2005). Discovery and selection of TMC114, a next generation HIV‐1 protease inhibitor. J. Med. Chem. 48: 1813–1822.

120 120 King, N.M., Prabu‐Jeyabalan, M., Nalivaika, E.A. et al. (2004). Structural and thermodynamic basis for the binding of TMC114, a next‐generation human immunodeficiency virus type 1 protease inhibitor. J. Virol. 78: 12012–12021.

121 121 Umezawa, H., Imoto, M., Sawa, T. et al. (1986). Studies on a new epidermal growth factor‐receptor kinase inhibitor, erbstatin, produced by MH435‐hF3. J. Antibiot. (Tokyo) 39: 170–173.

122 122 Mohammadi, M., McMahon, G., Sun, L. et al. (1997). Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276: 955–960.

123 123 Union, O.E. (2018). Health at a Glance: Europe 2018: State of Health in the EU Cycle, vol. 2020. Paris/Brussels: OECD Publishing/European Union.

124 124 NIH (2018). NIH Central Resource for Grants and Funding Information - Peer review, Vol. 2020, https://grants.nih.gov/grants/peer-review.htm (accessed 18 May 2020).