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Chemical approaches to the discovery and development of cancer therapies

Nature Reviews Cancer volume 5, pages 285–296 (2005)Cite this article

Key Points

  • The diverse roles of chemistry in the discovery of anticancer drugs include not only chemical synthesis, but an understanding of drug–target interactions and of the features of drug molecules that govern uptake and metabolism.

  • The role of chemistry in the development of anticancer drugs began with the mechanism-driven modification and synthesis of the nitrogen mustards.

  • Since the 1950s, several important drugs have been discovered by screening novel organic compounds and natural products using in vitro cell lines.

  • Structural biology and chemistry represent new approaches for discovering anticancer drugs, and are being used to determine the molecular aspects of kinase and protein–protein inhibition.

  • In silico screening can be used to screen large virtual libraries of compounds against the known structure of a target.

  • Molecules are being developed that selectively target a unique DNA sequence to inhibit transcription.

  • Synthetic medicinal chemistry has made important contributions to the development of targeted therapies and prodrugs — otherwise inactive compounds that are converted in tumour cells to active species.

  • Chemistry is essential for transforming 'lead molecules' into drugs. This requires optimizing the distribution, metabolism and excretion properties of a molecule as early as possible in the drug-discovery cycle.

Abstract

The chemical sciences are essential for the process of anticancer-drug discovery, and a range of chemical research techniques is needed to develop clinically effective drugs. Improved understanding of the cellular, molecular and genetic basis of cancer has increased the number of drug targets available. What chemical approaches are used to develop agents that target specific features of cancer cells and make these therapeutics more effective? We outline the roles that chemical synthesis and understanding of drug uptake have had in drug discovery over the past 100 years, as well as the chemical insights derived from knowledge of the three-dimensional structure of targets.

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Figure 1: Structures of mustards.
Figure 2: Temozolomide and its chemical reaction with DNA.
Figure 3: The principal steps in structure-based drug design using crystallography.
Figure 4: Nutlin-2.
Figure 5: New drugs targeting DNA.
Figure 6: The principles of antibody-dependent enzyme–prodrug therapy (ADEPT).
Figure 7: The principal steps in the medicinal chemistry of the discovery of imatinib (Glivec).

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References

  1. Gilman, A. G., Rall, T. W., Nies, A. S. & Taylor, P. (eds) Goodman and Gilman's The Pharmacological Basis of Therapeutics (Pergamon, New York, 1990).

    Google Scholar 

  2. Wani, M. C. Taylor, H. L., Wall, M. E., Coggon, P. & McPhail, A. T. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J. Am. Chem. Soc. 93, 2325–2327 (1971).

    CAS  PubMed  Google Scholar 

  3. Suffness, M. (ed.) Taxol: Science and Applications (CRC Press, Boca Raton, 1995).

    Google Scholar 

  4. Alley, M. C. et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 48, 589–601 (1988).

    CAS  PubMed  Google Scholar 

  5. Teicher, B. A. (ed.) Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval (Humana, New Jersey, 1997).

    Google Scholar 

  6. Stevens, M. F. G. et al. Antitumor imidazotetrazines. 1. synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin- 4(3h)-one, a novel broad-spectrum antitumor agent. J. Med. Chem. 27, 196–201 (1984). A key paper that describes the chemistry of temozolomide, an agent that is now in extensive clinical use against gliomas.

    CAS  PubMed  Google Scholar 

  7. Anslow, W. P., Karnofsky, D. A., Jager, B. V. & Smith, H. W. The intravenous, subcutaneous and cutaneous toxicity of bis((-chloroethyl) sulfide (mustard gas) and of various derivatives. J. Pharmacol. Exp. Ther. 93, 1–9 (1948)

    CAS  PubMed  Google Scholar 

  8. Rosenberg, B., van Camp, L., Trosko, J. & Mansour, V. Platinum compounds: a new class of potent antitumour agent. Nature 222, 385–386 (1969). The announcement of the initial discovery of cis -platinum.

    CAS  PubMed  Google Scholar 

  9. Rosenberg, B., van Camp, L. & Krigas, T. Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205, 698–699 (1965).

    CAS  PubMed  Google Scholar 

  10. Mann, J. Natural products in cancer chemotherapy: past, present and future. Nature Rev. Cancer 2, 143–148 (2002). Overview of the importance of natural products and their chemistry in the discovery of anticancer drugs.

    CAS  Google Scholar 

  11. Feher, M. & Schmidt, J. M. Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. J. Chem. Inf. Comput. Sci. 43, 218–227 (2003).

    CAS  PubMed  Google Scholar 

  12. Blundell, T. L. & Patel, S. High-throughput X-ray crystallography for drug discovery. Curr. Opin. Pharmacol. 4, 490–496 (2004).

    CAS  PubMed  Google Scholar 

  13. Kissau, L., Stahl, P., Mazitschek, R., Giannis, A. & Waldmann, H. Development of natural product-derived receptor tyrosine kinase inhibitors based on conservation of protein domain fold. J. Med. Chem. 46, 2917–2931 (2003).

    CAS  PubMed  Google Scholar 

  14. Ruetz, S., Fabbro, D., Zimmermann, J., Meyer, T. & Gray, N. Chemical and biological profile of dual Cdk1 and Cdk2 inhibitors. Curr. Med. Chem. Anti-Canc. Agents 3, 1–14 (2003).

    CAS  Google Scholar 

  15. Noble, M. E., Endicott, J. A. & Johnson, L. N. Protein kinase inhibitors: insights into drug design from structure. Science 303, 1800–1805 (2004).

    CAS  PubMed  Google Scholar 

  16. Diller, D. J. & Li, R. X. Kinases, homology models, and high throughput docking. J. Med. Chem. 46, 4638–4647 (2003).

    CAS  PubMed  Google Scholar 

  17. Capdeville, R., Buchdunger, E., Zimmermann, J. & Matter, A. Glivec (ST1571, imatinib), a rationally developed, targeted anticancer drug. Nature Rev. Drug Discov. 1, 493–502 (2002).

    CAS  Google Scholar 

  18. Demetri, G. D. et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. New Engl. J. Med. 347, 472–480 (2002).

    CAS  PubMed  Google Scholar 

  19. Heinrich, M. C. et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96, 925–932 (2000).

    CAS  PubMed  Google Scholar 

  20. Mol, C. D. et al. structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J. Biol. Chem. 279, 31655–31663 (2004).

    CAS  PubMed  Google Scholar 

  21. Daub, H., Specht, K. & Ullrich, A. Strategies to overcome resistance to targeted protein kinase inhibitors. Nature Rev. Drug Discov. 3, 1001–1010 (2004).

    CAS  Google Scholar 

  22. Lombardo, L. J. et al. Discovery of N-(2-chloro-6-methylphenyl)-2-(6-(4-(2- hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5 carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J. Med. Chem. 47, 6658–6661 (2004).

    CAS  PubMed  Google Scholar 

  23. Shah, N. P. et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305, 399–401 (2004).

    CAS  PubMed  Google Scholar 

  24. Bottger, A. et al. Molecular characterization of the hdm2–p53 interaction. J. Mol. Biol. 269, 744–756 (1997).

    CAS  PubMed  Google Scholar 

  25. Kussie, P. H. et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274, 948–953 (1996). Crystal-structure analysis of one of the most important protein–protein interaction complexes in cancer biology.

    CAS  PubMed  Google Scholar 

  26. Duncan, S. J. et al. Isolation and structure elucidation of chlorofusin, a novel p53–MDM2 antagonist from a Fusarium sp. J. Am. Chem. Soc. 123, 554–560 (2001).

    CAS  PubMed  Google Scholar 

  27. Duncan, S. J., Cooper, M. A. & Williams, D. H. Binding of an inhibitor of the p53/MDM2 interaction to MDM2. Chem. Commun. 316–317 (2003).

  28. Desai, P., Pfeiffer, S. S. & Boger, D. L. Synthesis of the chlorofusin cyclic peptide: assignment of the asparagine stereochemistry. Org. Lett. 5, 5047–5050 (2003).

    CAS  PubMed  Google Scholar 

  29. Malkinson, J. P. et al. Solid-phase synthesis of the cyclic peptide portion of chlorofusin, an inhibitor of p53–MDM2 interactions. Org. Lett. 5, 5051–5054 (2003).

    CAS  PubMed  Google Scholar 

  30. Galatin, P. S. & Abraham, D. J. A Non-peptidic sulfonamide inhibits the p53–mdm2 interaction and activates p53-dependent transcription in mdm2-overexpressing cells. J. Med. Chem. 47, 4163–4165 (2004).

    CAS  PubMed  Google Scholar 

  31. Vassilev, L. T. et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844–848 (2004). A key demonstration of success in targeting the p53–MDM2 interaction for potential anticancer therapy.

    CAS  PubMed  Google Scholar 

  32. Thurston, D. E. Nucleic acid targeting: therapeutic strategies for the 21st century. Br. J. Cancer 80, 65–85 (1999).

    CAS  PubMed  Google Scholar 

  33. Dervan, P. B. & Edelson, B. S. Recognition of the DNA minor groove by pyrrole-imidazole polyamides. Curr. Opin. Struc. Biol. 13, 284–299 (2003). An overview of sequence-specific DNA recognition by polyamide molecules, showing the substantial progress made in defining a general polyamide–DNA recognition code.

    CAS  Google Scholar 

  34. Best, T. P., Edelson, B. S., Nickols, N. G. & Dervan, P. B. Nuclear localization of pyrrole-imidazole polyamide-fluorescein conjugates in cell culture. Proc. Natl Acad. of Sci. USA 100, 12063–12068 (2003).

    CAS  Google Scholar 

  35. Wang, Y. D. et al. DNA crosslinking and biological activity of a hairpin polyamide-chlorambucil conjugate. Nucleic Acids Res. 31, 1208–1215 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Gregson, S. J. et al. Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity. J. Med. Chem. 44, 737–748 (2001). A chemically designed sequence-selective minor-groove-binding agent that is currently in Phase I clinical evaluation.

    CAS  PubMed  Google Scholar 

  37. Hartley, J. A. et al. SJG-136 (NSC 694501), a novel rationally designed DNA minor groove interstrand cross-linking agent with potent and broad spectrum antitumour activity: part 1: cellular pharmacology, in vitro and initial in vivo antitumor activity. Cancer Res. 64, 6693–6699 (2004).

    CAS  PubMed  Google Scholar 

  38. Pepper, C. J., Hambly, R. M., Fegan, C. D., Delavault, P. & Thurston, D. E. The novel sequence-specific dna cross-linking agent SJG-136 (NSC 694501) has potent and selective in vitro cytotoxicity in human B-cell chronic lymphocytic leukemia cells with evidence of a p53-independent mechanism of cell kill. Cancer Res. 64, 6750–6755 (2004).

    CAS  PubMed  Google Scholar 

  39. Alley, M. C. et al. SJG-136 (NSC 694501), a novel rationally designed dna minor groove interstrand cross-linking agent with potent and broad spectrum antitumour activity: part 2: efficacy evaluations. Cancer Res. 64, 6693–6699 (2004).

    PubMed  Google Scholar 

  40. Gregson, S. J. et al. Linker Length modulates dna cross-linking reactivity and cytotoxic potency of c8/c8′ ether-Linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers. J. Med. Chem. 47, 1161–1174 (2004).

    CAS  PubMed  Google Scholar 

  41. Kim, N. W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011–2015 (1994).

    CAS  PubMed  Google Scholar 

  42. Hahn, W. C. et al. Inhibition of telomerase limits the growth of human cancer cells. Nature Med. 10, 1164–1170 (1999).

    Google Scholar 

  43. Herbert, B. et al. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc. Natl Acad. Sci. USA 96, 14276–14281 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Neidle, S. & Parkinson, G. Telomere maintenance as a target for anticancer drug discovery. Nature Rev. Drug Discov. 1, 383–393 (2002). A survey of chemical approaches to telomerase inhibition in cancer.

    CAS  Google Scholar 

  45. Harrison, R. J. et al. Trisubstituted acridine derivatives as potent and selective telomerase inhibitors. J. Med. Chem. 46, 4463–4476 (2003).

    CAS  PubMed  Google Scholar 

  46. Read, M. et al. Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors. Proc. Natl Acad. Sci. USA 98, 4844–4849 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Incles, C. M. et al. A G-quadruplex telomere maintenance inhibitor produces p16-associated senescence and chromosomal fusions in human prostate cancer cells. Mol. Cancer Ther. 3, 1201–1206 (2004).

    CAS  PubMed  Google Scholar 

  48. Parkinson, G. N., Lee, M. P. H. & Neidle, S. Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 417, 876–880 (2002).

    CAS  PubMed  Google Scholar 

  49. Riou, J. F. et al. Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands. Proc. Natl Acad. Sci. USA 99, 2672–2677 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Burger, A. M. et al. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. Cancer Res. 65, 1489–1496 (2005).

    CAS  PubMed  Google Scholar 

  51. Anderson, A. C. The process of structure-based drug design. Chem. Biol. 10, 787–797 (2003).

    CAS  PubMed  Google Scholar 

  52. Ferrara, P., Gohlke, H., Price, D. J., Klebe, G. & Brooks, C. L. Assessing scoring functions for protein–ligand interactions. J. Med. Chem. 47, 3032–3047 (2004).

    CAS  PubMed  Google Scholar 

  53. Kang, X. S., Shafer, R. H. & Kuntz, I. D. Calculation of ligand-nucleic acid binding free energies with the generalized-Bom model in DOCK. Biopolymers 73, 192–204 (2004).

    CAS  PubMed  Google Scholar 

  54. Wang, R. X., Fang, X. L., Lu, Y. P. & Wang, S. M. The PDBbind database: collection of binding affinities for protein–ligand complexes with known three-dimensional structures. J. Med. Chem. 47, 2977–2980 (2004).

    CAS  PubMed  Google Scholar 

  55. Melton, R. G. & Knox, R. J. (eds) Enzyme–Prodrug Strategies for Cancer Therapy (Kluwer Academic/Plenum, New York, 1999).

    Google Scholar 

  56. Denny, W. A. Prodrug Strategies in Cancer Therapy. European J. Med. Chem. 36, 577–595 (2001). A comprehensive and authoritative survey of this field.

    CAS  Google Scholar 

  57. Bernstein, I. D. Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate. Leukemia 14, 474–475 (2000).

    CAS  PubMed  Google Scholar 

  58. Niculescu-Duvaz, I. Technology evaluation: gemtuzumab ozogamicin, celltech group. Curr. Opin. Mol. Ther. 2, 691–696 (2000).

    CAS  PubMed  Google Scholar 

  59. Niculescu-Duvaz, I., Friedlos, F., Niculescu-Duvaz, D., Davies, L. & Springer, C. J. Prodrugs for antibody- and gene-directed enzyme prodrug therapies (ADEPT and GDEPT). Anti-Cancer Drug Des. 14, 517–538 (1999).

    CAS  Google Scholar 

  60. Senter, P. D. & Springer, C. J. Selective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates. Adv. Drug Deliv. Rev. 53, 247–264 (2001).

    CAS  PubMed  Google Scholar 

  61. Springer, C. J. & Niculescuduvaz, I. Antibody-directed enzyme prodrug therapy (ADEPT) with mustard prodrugs. Anti-Cancer Drug Des. 10, 361–372 (1995).

    CAS  Google Scholar 

  62. Springer, C. J. & Niculescu–Duvaz, I. in Anticancer Drug Development (eds Baguely, B. C. & Kerr, D. J.) 137–152 (Academic, London, 2002).

    Google Scholar 

  63. Denny, W. A. Nitroreductase-based GDEPT. Curr. Pharm. Des. 8, 1349–1361 (2002).

    CAS  PubMed  Google Scholar 

  64. Dubowchik, G. M. & Walker, M. A. Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs. Pharm. Ther. 83, 67–123 (1999).

    CAS  Google Scholar 

  65. Bagshawe, K. D., Burke, P. J., Knox, R. J., Melton, R. G. & Sharma, S. K. Targeting enzymes to cancers new developments. Expert Opin. Investig. Drugs 8, 161–172 (1999).

    CAS  PubMed  Google Scholar 

  66. Webley, S. D. et al. Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material. Br. J. Cancer 84, 1671–1676 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Davis, A. M. & Riley, R. J. Predictive ADMET studies, the challenges and the opportunities. Curr. Opin. Chem. Biol. 8, 378–386 (2004).

    CAS  PubMed  Google Scholar 

  68. Blake, J. F. Chemoinformatics — predicting the physicochemical properties of 'drug-like' molecules. Curr. Opin. Biotechnol. 11, 104–107 (2000).

    CAS  PubMed  Google Scholar 

  69. Kelland, L. R. 'Of mice and men': values and liabilities of the athymic nude mouse model in anticancer drug development. Eur. J. Cancer 40, 827–836 (2004).

    CAS  PubMed  Google Scholar 

  70. Muegge, I., Heald, S. L. & Brittelli, D. Simple selection criteria for drug-like chemical matter. J. Med. Chem. 44, 1841–1846 (2001).

    CAS  PubMed  Google Scholar 

  71. Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23, 3–25 (1997). Enunciation of the Lepinski 'rule of five' for optimizing drug-like features in a molecule.

    CAS  Google Scholar 

  72. Vieth, M. et al. Characteristic physical properties and structural fragments of marketed oral drugs. J. Med. Chem. 47, 224–232 (2004).

    CAS  PubMed  Google Scholar 

  73. Ley, S. V. et al. Synthesis of the thapsigargins. Proc. Natl Acad. Sci. USA 101, 12073–12078 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Stockwell, B. R. Chemical genetics: ligand-based discovery of gene function. Nature Rev. Genet. 1, 116–125 (2000).

    CAS  PubMed  Google Scholar 

  75. Stockwell, B. R., Haggarty, S. J. & Schreiber, S. L. High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. Chem. Biol. 6, 71–83 (1999).

    CAS  PubMed  Google Scholar 

  76. Burke, M. D., Berger, E. M. & Schreiber, S. L. Generating diverse skeletons of small molecules combinatorially. Science 302, 613–618 (2003).

    CAS  PubMed  Google Scholar 

  77. Borisy, A. A. et al. Systematic discovery of multicomponent therapeutics. Proc. Natl Acad. Sci. USA 100, 7977–7982 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Futreal, P. A. et al. A census of human cancer genes. Nature Rev. Cancer 4, 177–183 (2004). An important starting point for choosing future targets for anticancer drugs.

    CAS  Google Scholar 

  79. Hurley, L. H. DNA and its associated processes as targets for cancer therapy. Nature Rev. Cancer 2, 188–200 (2002). A balanced review of the continuing importance of DNA as a therapeutic target in cancer.

    CAS  Google Scholar 

  80. Minter, A. R., Brennan, B. B. & Mapp, A. K. A small molecule transcriptional activation domain. J. Am. Chem. Soc. 126, 10504–10505 (2004).

    CAS  PubMed  Google Scholar 

  81. Huth, J. R. et al. NMR-driven discovery of benzoylanthranilic acid inhibitors of far upstream element binding protein binding to the human oncogene c-Myc promoter. J. Med. Chem. 47, 4851–4857 (2004).

    CAS  PubMed  Google Scholar 

  82. Williams, P. A. et al. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 305, 683–686 (2004). Structure of the first human CYP enzyme, which has an important role in drug metabolism.

    CAS  PubMed  Google Scholar 

  83. Chabner, B. A. & Roberts, T. G. Jr. Chemotherapy and the war on cancer. Nature Rev. Cancer 5, 65–72 (2005).

    CAS  Google Scholar 

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Acknowledgements

We are grateful to Cancer Research UK and its predecessor, Cancer Research Campaign, for its support of cancer-related chemistry over many years, and, in particular, to their support of work in our laboratories.

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Authors and Affiliations

  1. Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29–39 Brunswick Square, London, WC1N 1AX, UK

    Stephen Neidle

  2. Gene Targeted Drug Design Research Group, The School of Pharmacy, University of London, 29–39 Brunswick Square, London, WC1N 1AX, UK

    David E. Thurston

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Correspondence to Stephen Neidle.

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Competing interests

The authors are scientific advisors to the companies Antisoma Ltd (S.N.) and Spirogen Ltd (S.N. and D.E.T.), both of which are involved in the commercialization of anticancer agents. Both authors have a personal financial interest in Spirogen Ltd. S.N. receives research funding from Antisoma Ltd.

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DATABASES

Entrez Gene

ABL

BCR

BRCA1

BRCA2

CYP3A4

FBP

KIT

MDM2

p53

PDGFR

SRC

National Cancer Institute

brain tumours

breast cancer

chronic myeloid leukaemia

melanoma

prostate cancer

FURTHER INFORMATION

In Vitro Cell Line Screening Project

Kinasource

PDBbind database

Research Collaboratory Structural Bioinformatics Protein Data Bank

Zinc database

Glossary

SYNTHETIC CHEMISTRY

The creation of new molecules by means of a series of defined chemical reactions.

CREATIVE CHEMISTRY

The intellectually driven application of chemical principles.

PRODRUG

An inactive compound that is activated to a reactive drug species, preferably within target tumour cells, possibly by metabolism, selective action of a cancer-cell-specific enzyme, or by differences in pH/oxygenation between tumour and non-tumour tissue.

THERAPEUTIC INDEX

Ratio of the drug dosage that is required for toxic effect to the dosage required for therapeutic effect.

ALIPHATIC

An organic molecule that contains fully saturated carbon atoms. That is, a molecule without any aromaticity.

SN1 REACTION

Displacement of an atom or group by a nucleophilic atom or group; the process occurs as a unimolecular or bimolecular reaction, respectively.

STEREOCHEMISTRY

The three-dimensional relationship of atoms to each other in a molecule.

TOTAL CHEMICAL SYNTHESIS

The multistep synthesis of complex molecules, usually natural products, from simple precursors.

HIGH-THROUGHPUT

Automated processes of biological, biochemical or biophysical assay that examine very large numbers of compounds (or compound mixtures) on a short time scale, and enable active compounds to be rapidly identified.

SYNCHROTRON

A particle accelerator that can produce extremely intense X-rays, used for studying very small and/or poorly diffracting macromolecular crystals.

PHARMACOPHORE

The group of atoms in a drug molecule that are responsible for the pharmacological effects of the drug.

STRUCTURE–ACTIVITY RELATIONSHIPS

The relationships between chemical structure, chemical or physical properties and biological activity.

G-QUADRUPLEX

Formed at the telomeres by the association of four guanine-rich strands of DNA.

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Neidle, S., Thurston, D. Chemical approaches to the discovery and development of cancer therapies. Nat Rev Cancer 5, 285–296 (2005). https://doi.org/10.1038/nrc1587

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