Harnessing the knowledge of animal toxins to generate drugs

Pharmacological Research

Volumn 112, Issue , 2016, Pages 30-36

  Zambelli, V O ^a   Pasqualoto, K F M ^a   Picolo, G ^a   Chudzinski Tavassi, A M ^a   Cury, Y ^a  

^a INSTITUTO BUTANTAN   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

BATROXOBIN; BEE VENOM; BOMBESIN; BOTROCETIN; CAPTOPRIL; CENDERITIDE; CHLOROTOXIN; CHOLINERGIC RECEPTOR BLOCKING AGENT; CROTOXIN; DESMOTEPLASE; DRUG; ECARIN; EPTIFIBATIDE; EXENDIN 4; FIBRIN GLUE; HIRULOG; MAMBALGIN; MELITTIN; METALLOPROTEINASE; OMEGA CONOTOXIN CVID; OMEGA CONOTOXIN MVIIA; POTASSIUM CHANNEL BLOCKING AGENT; RPI 78M; SECRETORY PHOSPHOLIPASE A2; SHK 192; SNAIL VENOM; SPIDER VENOM; TIROFIBAN; TOXIN; UNCLASSIFIED DRUG; PEPTIDE; VENOM;

ACUTE CORONARY SYNDROME; ADRENOLEUKODYSTROPHY; ADVANCED CANCER; AMYOTROPHIC LATERAL SCLEROSIS; ANALGESIC ACTIVITY; ANTICOAGULATION; ANTINOCICEPTION; APOPTOSIS; ARTHRITIS; ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; BRAIN ISCHEMIA; COGNITIVE DEFECT; CONGESTIVE HEART FAILURE; DIZZINESS; DRUG DESIGN; DRUG SCREENING; DRUG STRUCTURE; DRUG TARGETING; HEART DISEASE; HEMOSTASIS; HUMAN; HYPERTENSION; INTRACTABLE PAIN; MULTIPLE SCLEROSIS; MYASTHENIA GRAVIS; NAUSEA; NEUROLOGIC DISEASE; NEUROPATHIC PAIN; NEUROTOXICITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NYSTAGMUS; PANCREATITIS; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; SOLID TUMOR; TRANSCRIPTOMICS; ANIMAL; CHEMISTRY; CHRONIC PAIN; DRUG DEVELOPMENT; MOLECULARLY TARGETED THERAPY; NEOPLASMS; THROMBOSIS;

ANIMALS; CHRONIC PAIN; DRUG DISCOVERY; HUMANS; HYPERTENSION; MOLECULAR TARGETED THERAPY; NEOPLASMS; PEPTIDES; THROMBOSIS; TOXINS, BIOLOGICAL; VENOMS;

EID: 84956695987     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2016.01.009     Document Type: Review

References (83)

1. [1] King, G.F., Venoms as a platform for human drugs: translating toxins into therapeutics. Expert Opin. Biol. Ther. 11 (2011), 1469–1484.
2. [2] Cury, Y., Picolo, G., Animal toxins as analgesics-an overview. Drug News Perspect. 19 (2006), 381–392.
3. [3] Harvey, A.L., Toxins and drug discovery. Toxicon 92 (2014), 193–200.
4. [4] Kinch, M.S., Haynesworth, A., Kinch, S.L., Hoyer, D., An overview of FDA-approved new molecular entities: 1827–2013. Drug Discov. Today 19 (2014), 1033–1039.
5. [5] Smith, C.G., Vane, J.R., The discovery of captopril. FASEB J. 17 (2003), 788–789.
6. [6] Bryan, J., From snake venom to ace inhibitor—the discovery and rise of captopril. Pharm. J., 2009.
7. [7] Ferreira, S.H., A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. Br. J. Pharm. Chemother. 24 (1965), 163–169.
8. [8] Wermuth, C., The Practice of Medicinal Chemistry. 2008, Academic Press.
9. [9] Cushman, D.W., Cheung, H.S., Sabo, E.F., Ondetti, M.A., Design of potent competitive inhibitors of angiotensin-converting enzyme: carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry 16 (1977), 5484–5491.
10. [10] Patrick, Graham L., An Introduction to Medicinal Chemistry. fourth edition, 2010, Oxford.
11. [11] Berman, H.M., Bhat, T.N., Bourne, P.E., Feng, Z., Gilliland, G., Weissig, H., Westbrook, J., The protein data bank and the challenge of structural genomics. Nat. Struct. Biol.(Suppl. 7), 2000, 957–959.
12. [12] Molinski, T.F., Dalisay, D.S., Lievens, S.L., Saludes, J.P., Drug development from marine natural products. Nat. Rev. Drug Discov. 8 (2009), 69–85.
13. [13] McGivern, J.G., Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr. Dis. Treat. 3 (2007), 69–85.
14. [14] Rauck, R.L., Wallace, M.S., Burton, A.W., Kapural, L., North, J.M., Intrathecal ziconotide for neuropathic pain: a review. Pain Pract. 9 (2009), 327–337.
15. [15] O'Shea, J.C., Tcheng Eptifibatide, J.E., A potent inhibitor of the platelet receptor integrin glycoprotein iib/iiia. Expert Opin. Pharmacother. 3 (2002), 1199–1210.
16. [16] Menozzi, A., Merlini, P.A., Ardissino, D., Tirofiban in acute coronary syndromes. Expert Rev. Cardiovasc. Ther. 3 (2005), 193–206.
17. [17] Chandrasekhar, J., Mehran, R., The ideal anticoagulation strategy in ST-elevation myocardial infarction. Prog. Cardiovasc. Dis. 58 (2015), 247–259.
18. [18] Valgimigli, M., Frigoli, E., Leonardi, S., Rothenbuhler, M., Gagnor, A., Calabro, P., Garducci, S., Rubartelli, P., Briguori, C., Ando, G., Repetto, A., Limbruno, U., Garbo, R., Sganzerla, P., Russo, F., Lupi, A., Cortese, B., Ausiello, A., Ierna, S., Esposito, G., Presbitero, P., Santarelli, A., Sardella, G., Varbella, F., Tresoldi, S., de Cesare, N., Rigattieri, S., Zingarelli, A., Tosi, P., van‘t Hof, A., Boccuzzi, G., Omerovic, E., Sabate, M., Heg, D., Juni, P., Vranckx, P., Investigators, M., Bivalirudin or unfractionated heparin in acute coronary syndromes. N. Eng. J. Med. 373 (2015), 997–1009.
19. [19] Goud, A., Zhong, J., Rajagopalan, S., Emerging utility of once-weekly exenatide in patients with type 2 diabetes. Diab. Metab. Syndrome Obesity Targets Ther. 8 (2015), 505–512.
20. [20] Veiseh, M., Gabikian, P., Bahrami, S.B., Veiseh, O., Zhang, M., Hackman, R.C., Ravanpay, A.C., Stroud, M.R., Kusuma, Y., Hansen, S.J., Kwok, D., Munoz, N.M., Sze, R.W., Grady, W.M., Greenberg, N.M., Ellenbogen, R.G., Olson, J.M., Tumor paint: a chlorotoxin: Cy5: 5 bioconjugate for intraoperative visualization of cancer foci. Cancer Res. 67 (2007), 6882–6888.
21. [21] Kesavan, K., Ratliff, J., Johnson, E.W., Dahlberg, W., Asara, J.M., Misra, P., Frangioni, J.V., Jacoby, D.B., Annexin a2 is a molecular target for tm601, a peptide with tumor-targeting and anti-angiogenic effects. J. Biol. Chem. 285 (2010), 4366–4374.
22. [22] Lewis, R.J., Nielsen, K.J., Craik, D.J., Loughnan, M.L., Adams, D.A., Sharpe, I.A., Luchian, T., Adams, D.J., Bond, T., Thomas, L., Jones, A., Matheson, J.L., Drinkwater, R., Andrews, P.R., Alewood, P.F., Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J. Biol. Chem. 275 (2000), 35335–35344.
23. [23] Jayamanne, A., Jeong, H.J., Schroeder, C.I., Lewis, R.J., Christie, M.J., Vaughan, C.W., Spinal actions of omega-conotoxins, CVID, MVIIA and related peptides in a rat neuropathic pain model. Br. J. Pharmacol. 170 (2013), 245–254.
24. [24] Groeneveld G., 2013. Available from: https://isctm.org/public_access/Oct_2013/presentations/2013_Autumn_Groeneveld.pdf.
25. [25] Clark, R.J., Akcan, M., Kaas, Q., Daly, N.L., Craik, D.J., Cyclization of conotoxins to improve their biopharmaceutical properties. Toxicon 59 (2012), 446–455.
26. [26] Yu, R., Seymour, V.A., Berecki, G., Jia, X., Akcan, M., Adams, D.J., Kaas, Q., Craik, D.J., Less is more: design of a highly stable disulfide-deleted mutant of analgesic cyclic alpha-conotoxin VC1.1. Sci. Rep., 5, 2015, 13264.
27. [27] Vieira, L.B., Kushmerick, C., Hildebrand, M.E., Garcia, E., Stea, A., Cordeiro, M.N., Richardson, M., Gomez, M.V., Snutch, T.P., Inhibition of high voltage-activated calcium channels by spider toxin PNTx3-6. J. Pharmacol. Exp. Ther. 314 (2005), 1370–1377.
28. [28] Souza, A.H., Ferreira, J., Cordeiro Mdo, N., Vieira, L.B., De Castro, C.J., Trevisan, G., Reis, H., Souza, I.A., Richardson, M., Prado, M.A., Prado, V.F., Gomez, M.V., Analgesic effect in rodents of native and recombinant Phalpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. Pain 140 (2008), 115–126.
29. [29] Silva, R.B., Sperotto, N.D., Andrade, E.L., Pereira, T.C., Leite, C.E., de Souza, A.H., Bogo, M.R., Morrone, F.B., Gomez, M.V., Campos, M.M., Spinal blockage of P/Q- or N-type voltage-gated calcium channels modulates functional and symptomatic changes related to haemorrhagic cystitis in mice. Br. J. Pharmacol. 172 (2015), 924–939.
30. [30] Nunes, K.P., Costa-Goncalves, A., Lanza, L.F., Cortes, S.F., Cordeiro, M.N., Richardson, M., Pimenta, A.M., Webb, R.C., Leite, R., De Lima, M.E., Tx2-6 toxin of the Phoneutria nigriventer spider potentiates rat erectile function. Toxicon 51 (2008), 1197–1206.
31. [31] McCarthy, C.A., Rash, L.D., Chassagnon, I.R., King, G.F., Widdop, R.E., PcTx1 affords neuroprotection in a conscious model of stroke in hypertensive rats via selective inhibition of asic1a. Neuropharmacology 99 (2015), 650–657.
32. [32] Yang, X., Lu, X., Wang, L., Chen, S., Li, J., Cao, J., Chen, J., Hao, Y., Li, Y., Zhao, L., Li, H., Liu, D., Wang, L., Lu, F., Shen, C., Yu, L., Wu, X., Zhao, Q., Ji, X., Guo, D., Peng, X., Huang, J., Gu, D., Common variants at 12q24 are associated with drinking behavior in han chinese. Am. J. Clin. Nutr. 97 (2013), 545–551.
33. [33] Diochot, S., Baron, A., Salinas, M., Douguet, D., Scarzello, S., Dabert-Gay, A.S., Debayle, D., Friend, V., Alloui, A., Lazdunski, M., Lingueglia, E., Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature 490 (2012), 552–555.
34. [34] Moreno, M., Giralt, E., Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. Toxins 7 (2015), 1126–1150.
35. [35] Wooddell, C.I., Rozema, D.B., Hossbach, M., John, M., Hamilton, H.L., Chu, Q., Hegge, J.O., Klein, J.J., Wakefield, D.H., Oropeza, C.E., Deckert, J., Roehl, I., Jahn-Hofmann, K., Hadwiger, P., Vornlocher, H.P., McLachlan, A., Lewis, D.L., Hepatocyte-targeted RNAi therapeutics for the treatment of chronic hepatitis b virus infection. Mol. Ther. 21 (2013), 973–985.
36. [36] Q L, Z, Z, C H. Polypeptide carrying melittin, nanoparticle carrying melittin and use thereof. WO/2013/135103, 19 September 2013.
37. [37] Hong, H., Zhang, Y., Sun, J., Cai, W., Positron emission tomography imaging of prostate cancer. Amino Acids 39 (2010), 11–27.
38. [38] Pennington, M.W., Chang, S.C., Chauhan, S., Huq, R., Tajhya, R.B., Chhabra, S., Norton, R.S., Beeton, C., Development of highly selective Kv1. 3-blocking peptides based on the sea anemone peptide shk. Marine Drugs 13 (2015), 529–542.
39. [39] Lee, C.Y., Chen, H.H., Lisy, O., Swan, S., Cannon, C., Lieu, H.D., Burnett, J.C. Jr., Pharmacodynamics of a novel designer natriuretic peptide, CD-NP, in a first-in-human clinical trial in healthy subjects. J. Clin. Pharmacol. 49 (2009), 668–673.
40. [40] Receptopharm, Inc., Modified elapid venoms as stimulators of the immune reaction, US7758894, 2006.
41. [41] Wei, J.M., Zhu, M.W., Zhang, Z.T., Jia, Z.G., He, X.D., Wan, Y.L., Wang, S., Xiu, D.R., Tang, Y., Li, J., Xu, J.Y., Heng, Q.S., A multicenter, phase III trial of hemocoagulase agkistrodon: Hemostasis, coagulation, and safety in patients undergoing abdominal surgery. Chin. Med. J. 123 (2010), 589–593.
42. [42] Shetty, V., Sriram, S.G., Effectiveness of intravenous haemocoagulase on haemorrhage control in bi-maxillary orthognathic surgery-a prospective, randomised, controlled, double-blind study. J. Craniomaxillofac. Surg. 43 (2015), 2000–2003.
43. [43] Albers, G.W., von Kummer, R., Truelsen, T., Jensen, J.K., Ravn, G.M., Gronning, B.A., Chabriat, H., Chang, K.C., Davalos, A.E., Ford, G.A., Grotta, J., Kaste, M., Schwamm, L.H., Shuaib, A., Investigators D-safety and efficacy of desmoteplase given 3–9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (dias-3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Neurol. 14 (2015), 575–584.
44. [44] Cura, J.E., Blanzaco, D.P., Brisson, C., Cura, M.A., Cabrol, R., Larrateguy, L., Mendez, C., Sechi, J.C., Silveira, J.S., Theiller, E., de Roodt, A.R., Vidal, J.C., Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), nsc-624244) in patients with advanced cancer. Clin. Cancer Res. 8 (2002), 1033–1041.
45. [45] Castro, F.R., Farias, A.S., Proenca, P.L., de La Hoz, C., Langone, F., Oliveira, E.C., Toyama, M.H., Marangoni, S., Santos, L.M., The effect of treatment with crotapotin on the evolution of experimental autoimmune neuritis induced in lewis rats. Toxicon 49 (2007), 299–305.
46. [46] Nogueira-Neto Fde, S., Amorim, R.L., Brigatte, P., Picolo, G., Ferreira, W.A. Jr., Gutierrez, V.P., Conceicao, I.M., Della-Casa, M.S., Takahira, R.K., Nicoletti, J.L., Cury, Y., The analgesic effect of crotoxin on neuropathic pain is mediated by central muscarinic receptors and 5-lipoxygenase-derived mediators. Pharmacol. Biochem. Behav. 91 (2008), 252–260.
47. [47] Sampaio, S.C., Hyslop, S., Fontes, M.R., Prado-Franceschi, J., Zambelli, V.O., Magro, A.J., Brigatte, P., Gutierrez, V.P., Cury Crotoxin, Y., Novel activities for a classic beta-neurotoxin. Toxicon 55 (2010), 1045–1060.
48. [48] Almeida Cde, S., Andrade-Oliveira, V., Camara, N.O., Jacysyn, J.F., Faquim-Mauro, E.L., Crotoxin from crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice. PLoS One, 10, 2015, e0121427.
49. ® (gefinitib) in human lung adenocarcinoma spca1 cells. Molecular Med. Rep. 10 (2014), 3009–3014.
50. [50] Favoretto, B.C., Ricardi, R., Silva, S.R., Jacysyn, J.F., Fernandes, I., Takehara, H.A., Faquim-Mauro, E.L., Immunomodulatory effects of crotoxin isolated from Crotalus durissus terrificus venom in mice immunised with human serum albumin. Toxicon 57 (2011), 600–607.
51. [51] Lima, T.S., Cataneo, S.C., Iritus, A.C., Sampaio, S.C., Della-Casa, M.S., Cirillo, M.C., Crotoxin, a rattlesnake toxin, induces a long-lasting inhibitory effect on phagocytosis by neutrophils. Exp. Biol. Med. 237 (2012), 1219–1230.
52. [52] https://clinicaltrials.gov/ct2/show/NCT01481532?term=crotoxin&rank=1.
53. [53] Camargo, E.A., Esquisatto, L.C., Esquisatto, M.A., Ribela, M.T., Cintra, A.C., Giglio, J.R., Antunes, E., Landucci, E.C., Characterization of the acute pancreatitis induced by secretory phospholipases A2 in rats. Toxicon 46 (2005), 921–926.
54. [54] Sonoki, K., Iwase, M., Sasaki, N., Ohdo, S., Higuchi, S., Takata, Y., Iida, M., Secretory PLA2 inhibitor indoxam suppresses LDL modification and associated inflammatory responses in TNFalpha-stimulated human endothelial cells. Br. J. Pharmacol. 153 (2008), 1399–1408.
55. [55] Fernandes, C.M., Pereira Teixeira Cde, F., Leite, A.C., Gutierrez, J.M., Rocha, F.A., The snake venom metalloproteinase bap1 induces joint hypernociception through TNF-alpha and PGE2-dependent mechanisms. Br. J. Pharmacol. 151 (2007), 1254–1261.
56. [56] Sun, X., Cao, W., Cui, J., Wang, L., Ma, L., Wang, T., Peng, C., Tian, Z., Shi, S., Guo, S., Tian, Y., An animal model of atherosclerotic plaque disruption and thrombosis in rabbit using pharmacological triggering to plaques induced by perivascular collar placement. Cardiovasc. Pathol. 22 (2013), 264–269.
57. [57] Funk, C., Gmur, J., Herold, R., Straub, P.W., Reptilase-R—a new reagent in blood coagulation. Br. J. Haematol. 21 (1971), 43–52.
58. [58] Weinger, R.S., Rudy, C., Moake, J.L., Olson, J.D., Cimo, P.L., Prothrombin houston: a dysprothrombin identifiable by crossed immunoelectrofocusing and abnormal Echis carinatus venom activation. Blood 55 (1980), 811–816.
59. [59] Di Scipio, R.G., Hermodson, M.A., Davie, E.W., Activation of human factor X (Stuart factor) by a protease from Russell's viper venom. Biochemistry 16 (1977), 5253–5260.
60. [60] Stocker, K., Fischer, H., Meier, J., Brogli, M., Svendsen, L., Characterization of the protein C activator protac from the venom of the southern copperhead (Agkistrodon contortrix) snake. Toxicon 25 (1987), 239–252.
61. [61] Usami, Y., Fujimura, Y., Suzuki, M., Ozeki, Y., Nishio, K., Fukui, H., Titani, K., Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca. Proc. Natl. Acad. Sci. U. S. A. 90 (1993), 928–932.
62. [62] Rishton, G.M., Natural products as a robust source of new drugs and drug leads: past successes and present day issues. Am. J. Cardiol. 101 (2008), 43D–49D.
63. [63] Zheng, W., Thorne, N., McKew, J.C., Phenotypic screens as a renewed approach for drug discovery. Drug Discov. Today 18 (2013), 1067–1073.
64. [64] Wehling, M., Assessing the translatability of drug projects: what needs to be scored to predict success. Nat. Rev. Drug Discov. 8 (2009), 541–546.
65. [65] Gutierrez, V.P., Konno, K., Chacur, M., Sampaio, S.C., Picolo, G., Brigatte, P., Zambelli, V.O., Cury, Y., Crotalphine induces potent antinociception in neuropathic pain by acting at peripheral opioid receptors. Eur. J. Pharmacol. 594 (2008), 84–92.
66. [66] Konno, K., Picolo, G., Gutierrez, V.P., Brigatte, P., Zambelli, V.O., Camargo, A.C., Cury, Y., Crotalphine, a novel potent analgesic peptide from the venom of the south american rattlesnake Crotalus durissus terrificus. Peptides 29 (2008), 1293–1304.
67. [67] Machado, F.C., Zambelli, V.O., Fernandes, A.C., Heimann, A.S., Cury, Y., Picolo, G., Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine. Br. J. Pharmacol. 171 (2014), 961–972.
68. [68] Batista, I.F., Ramos, O.H., Ventura, J.S., Junqueira-de-Azevedo, I.L., Ho, P.L., Chudzinski-Tavassi, A.M., A new factor Xa inhibitor from Amblyomma cajennense with a unique domain composition. Arch. Biochem. Biophys. 493 (2010), 151–156.
69. [69] Pasqualoto, K.F., Balan, A., Barreto, S.A., Simons, S.M., Chudzinski-Tavassi, A.M., Structural findings and molecular modeling approach of a TFPI-like inhibitor. Protein Pept. Lett. 21 (2014), 452–457.
70. [70] Ventura, J.S., Faria, F., Batista, I.F., Simons, S.M., Oliveira, D.G., Morais, K.L., Chudzinski-Tavassi, A.M., A kunitz-type FXa inhibitor affects tumor progression, hypercoagulable state and triggers apoptosis. Biomed. Pharmacother. 67 (2013), 192–196.
71. [71] Chudzinski-Tavassi, A.M., De-Sa-Junior, P.L., Simons, S.M., Maria, D.A., de Souza Ventura, J., Batista, I.F., Faria, F., Duraes, E., Reis, E.M., Demasi, M., A new tick kunitz type inhibitor, amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system. Toxicon 56 (2010), 1145–1154.
72. [72] Pacheco, M.T., Berra, C.M., Morais, K.L., Sciani, J.M., Branco, V.G., Bosch, R.V., Chudzinski-Tavassi, A.M., Dynein function and protein clearance changes in tumor cells induced by a kunitz-type molecule, amblyomin-X. PLoS One, 9, 2014, e111907.
73. [73] Giacomotto, J., Segalat, L., High-throughput screening and small animal models, where are we. Br. J. Pharmacol. 160 (2010), 204–216.
74. [74] Ferreira, A.S., Barraviera, B., Barraviera, S.R., Abbade, L.P., Caramori, C.A., Ferreira, R.S. Jr., A success in toxinology translational research in brazil: bridging the gap. Toxicon 69 (2013), 50–54.
75. [75] Vanscheidt, W., Ukat, A., Horak, V., Bruning, H., Hunyadi, J., Pavlicek, R., Emter, M., Hartmann, A., Bende, J., Zwingers, T., Ermuth, T., Eberhardt, R., Treatment of recalcitrant venous leg ulcers with autologous keratinocytes in fibrin sealant: a multinational randomized controlled clinical trial. Wound Repair Regen. 15 (2007), 308–315.
76. [76] Vetter, I., Davis, J.L., Rash, L.D., Anangi, R., Mobli, M., Alewood, P.F., Lewis, R.J., Venomics, King G.F., A new paradigm for natural products-based drug discovery. Amino Acids 40 (2011), 15–28.
77. [77] Lombardino, J.G., Lowe, J.A. 3rd, The role of the medicinal chemist in drug discovery-then and now. Nat. Rev. Drug Discov. 3 (2004), 853–862.
78. [78] Drews, J., Drug discovery: a historical perspective. Science 287 (2000), 1960–1964.
79. [79] Sams-Dodd, F., Drug discovery: selecting the optimal approach. Drug Discov. Today 11 (2006), 465–472.
80. [80] Schneider, M., A rational approach to maximize success rate in target discovery. Arch. Pharm. (Weinheim) 337 (2004), 625–633.
81. [81] Betz, U.A., How many genomics targets can a portfolio afford. Drug Discov. Today 10 (2005), 1057–1063.
82. [82] Hajduk, P.J., Huth, J.R., Tse, C., Predicting protein druggability. Drug Discov. Today 10 (2005), 1675–1682.
83. [83] Batista, I.F., et al. Expressed sequence tags (ESTs) from the salivary glands of the tick Amblyomma cajennense (Acari: Ixodidae). Toxicon 51:5 (2008), 823–834.