Natural products as sources of new drugs over the period 1981–2002
Abstract
This review is an updated and expanded version of a paper that was published in this journal in 1997. The time frame has been extended in both directions to include the 22 years from 1981 to 2002, and a new secondary subdivision related to the natural product source but applied to formally synthetic compounds has been introduced, using the concept of a "natural product mimic" or "NM" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame. In other areas, the influence of natural product structures is quite marked, particularly in the antihypertensive area, where of the 74 formally synthetic drugs, 48 can be traced to natural product structures/mimics. Similarly, with the 10 antimigraine drugs, seven are based on the serotonin molecule or derivatives thereof. Finally, although combinatorial techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of a number of recently approved agents, we have not been able to identify a de novo combinatorial compound approved as a drug in this time frame.
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Natural products represent an available source of new drugs, drug leads and chemical entities.
“Natural products represent an available source of new drugs, drug leads and chemical entities [11,12].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [12]
Cites
Abramson, M. H. (1996) · The Endocrinologist · doi:10.1097/00019616-199603000-00014 · Cited by 1,411 · see citing works
The influence of natural products upon drug discovery (Antiquity to late 1999)
Newman, D. J., Cragg, G. M., & Snader, K. M. (2000) · Natural Product Reports · doi:10.1039/a902202c · Cited by 1,293 · see citing works
Self-citationNatural products in cancer chemotherapy: past, present and future
Mann, J. (2002) · Nature reviews. Cancer · doi:10.1038/nrc723 · Cited by 685 · see citing works
Angiotensin Receptors and Their Antagonists
Goodfriend, T. L., Elliott, M. E., & Catt, K. J. (1996) · New England Journal of Medicine · doi:10.1056/nejm199606203342507 · Cited by 560 · see citing works
Zdobnov, E. M., von Mering, C., Letunic, I., Torrents, D., Suyama, M., Copley, R. R., Christophides, G. K., Thomasova, D., Holt, R. A., Subramanian, G. M., et al. (2002) · Science · doi:10.1126/science.1077061 · Cited by 553 · see citing works
Carini, D. J., Duncia, J. V., Aldrich, P. E., et al. (1991) · Journal of Medicinal Chemistry · doi:10.1021/jm00112a031 · Cited by 436 · see citing works
Protein kinases as targets for anticancer agents: from inhibitors to useful drugs
Fabbro, D., Ruetz, S., Buchdunger, E., Cowan‐Jacob, S. W., Fendrich, G., Liebetanz, J., Mestan, J., O'Reilly, T., Traxler, P., Chaudhuri, B., et al. (2002) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00179-1 · Cited by 336 · see citing works
Duncia, J. V., Chiu, A. T., Carini, D. J., et al. (1990) · Journal of Medicinal Chemistry · doi:10.1021/jm00167a007 · Cited by 242 · see citing works
Annual Reports in Medicinal Chemistry, 1965.
Burger, A. (1967) · Journal of Medicinal Chemistry · doi:10.1021/jm00316a057 · Cited by 237 · see citing works
Peptidomimetics derived from natural products
Wiley, R. A., & Rich, D. H. (1993) · Medicinal Research Reviews · doi:10.1002/med.2610130305 · Cited by 218 · see citing works
Pelish, H. E., Westwood, N. J., Feng, Y., et al. (2001) · Journal of the American Chemical Society · doi:10.1021/ja016093h · Cited by 208 · see citing works
Microbial natural products as a source of antifungals
Vicente, M. F., Basilio, Á., Cabello, A., & Peláez, F. (2003) · Clinical Microbiology and Infection · doi:10.1046/j.1469-0691.2003.00489.x · Cited by 191 · see citing works
Selecting protein tyrosine phosphatases as drug targets
van Huijsduijnen, R. H., Bombrun, A., & Swinnen, D. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(02)02438-8 · Cited by 166 · see citing works
Natural Products and Derivatives as Leads to Cell Cycle Pathway Targets in Cancer Chemotherapy
Newman, D. M., Cragg, G. M. L., Holbeck, S. L., et al. (2002) · Current Cancer Drug Targets · doi:10.2174/1568009023333791 · Cited by 160 · see citing works
Self-citationNiederhuber, J. E. (1993) · B.C. Decker eBooks · Cited by 151 · see citing works
Zimmermann, J., Buchdunger, E., Mett, H., et al. (1996) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/0960-894x(96)00197-7 · Cited by 146 · see citing works
A New Global Effort to Control Malaria
Sachs, J. (2002) · Science · doi:10.1126/science.1077900 · Cited by 113 · see citing works
N’Goka, V., Schlewer, G., Linget, J. M., et al. (1991) · Journal of Medicinal Chemistry · doi:10.1021/jm00112a032 · Cited by 93 · see citing works
Combinatorial synthesis of natural products
Nielsen, J. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00330-7 · Cited by 86 · see citing works
Natural Product Guided Compound Library Development
Breinbauer, R., Manger, M., Scheck, M., et al. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023368773 · Cited by 82 · see citing works
Carini, D. J., Duncia, J. V., Johnson, A. L., et al. (1990) · Journal of Medicinal Chemistry · doi:10.1021/jm00167a008 · Cited by 80 · see citing works
Fulfilling the promise of biotechnology
Colwell, R. R. (2002) · Biotechnology Advances · doi:10.1016/s0734-9750(02)00011-3 · Cited by 64 · see citing works
Synthesis and Enzyme Inhibitory Activities of Novel Peptide Isosteres
Venkatesan, N., & Kim, B. H. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023368692 · Cited by 52 · see citing works
Molecular Modeling in the Design of Peptidomimetics and Peptide Surrogates
Pérez, J. J., Corcho, F. J., & Llorens, O. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023368683 · Cited by 34 · see citing works
Chapter 28. To market, to market — 2000
Gaudillière, B., Bernardelli, P., & Berna, P. P. (2001) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(01)36068-2 · Cited by 28 · see citing works
Chapter 26. To market, to market - 2001
Bernardelli, P., Gaudillière, B., & Vergne, F. (2002) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(02)37027-1 · Cited by 26 · see citing works
Chapter 34. To Market, To Market - 1995
Cheng, X. (1996) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60473-x · Cited by 24 · see citing works
Chapter 34. To Market, To Market - 1993
Cheng, X. (1994) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60747-2 · Cited by 23 · see citing works
KOYAMA, G. (1974) · Helvetica Chimica Acta · doi:10.1002/hlca.19740570819 · Cited by 21 · see citing works
Section VII. Trends and perspectives
Gaudillière, B., & Berna, P. P. (2000) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(00)35031-x · Cited by 20 · see citing works
Chapter 31. To Market, To Market - 1990
Strupczewski, J. D., Ellis, D. B., & Allen, R. C. (1991) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)61218-x · Cited by 18 · see citing works
Class, S. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n048.p039 · Cited by 18 · see citing works
Chapter 34. To Market, To Market – 1992
Strupczewski, J. D., & Ellis, D. B. (1993) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60904-5 · Cited by 17 · see citing works
Goss, W. A., & Cook, T. M. (1975) · Springer eBooks · doi:10.1007/978-3-642-46304-4_12 · Cited by 16 · see citing works
Chapter 33. To Market, To Market - 1991
Strupczewski, J. D., & Ellis, D. B. (1992) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60431-5 · Cited by 15 · see citing works
Chapter 31. To Market, To Market -1988
Ong, H. H., & Allen, R. C. (1989) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60553-9 · Cited by 14 · see citing works
ORGANIC LAB SPARKS DRUG DISCOVERY
BORMAN, S. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n002.p023 · Cited by 12 · see citing works
BORMAN, S. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n045.p043 · Cited by 11 · see citing works
Chapter 33. To Market, To Market – 1987
Ong, H. H., & Allen, R. C. (1988) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60861-1 · Cited by 11 · see citing works
Chapter 33. To Market, To Market - 1989
Ong, H. H., & Allen, R. C. (1990) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)61609-7 · Cited by 8 · see citing works
PRECAUTIONARY PRINCIPLE DEBATE
HILEMAN, Β. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n016.p024 · Cited by 7 · see citing works
Barrett, V. L. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n003.p050 · Cited by 1 · see citing works
CHF HOSTS MULTIPLE CELEBRATIONS
Reisch, M. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n031.p049 · Cited by 1 · see citing works
HOW TO GET SOMEONE TO READ YOUR PAPER
WILKINSON, S. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n018.p057 · Cited by 1 · see citing works
BORMAN, S. (2002) · Chemical & Engineering News · doi:10.1021/cen-v080n041.p047 · Cited by 1 · see citing works
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Newman, D. J., & Cragg, G. M. (2007) · Journal of Natural Products · doi:10.1021/np068054v · Cited by 5,517 · see citing works
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Hernandes, M., Cavalcanti, S. M., Moreira, D. R., de Azevedo Junior, W., & Leite, A. C. (2010) · Current Drug Targets · doi:10.2174/138945010790711996 · Cited by 723 · see citing works
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Tan, D. S. (2005) · Nature Chemical Biology · doi:10.1038/nchembio0705-74 · Cited by 605 · see citing works
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Simmons, T. L., Andrianasolo, E., McPhail, K., Flatt, P., & Gerwick, W. H. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.333.4.2 · Cited by 597 · see citing works
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Khalifa, S. A. M., Elias, N., Farag, M. A., Chen, L., Saeed, A., Hegazy, M.-E. F., Moustafa, M. S., Abd El-Wahed, A., Al-Mousawi, S. M., Musharraf, S. G., et al. (2019) · Marine Drugs · doi:10.3390/md17090491 · Cited by 555 · see citing works
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BackgroundCyanobacteria: an emerging source for drug discovery
Singh, R. K., Tiwari, S. P., Rai, A. K., & Mohapatra, T. M. (2011) · The Journal of Antibiotics · doi:10.1038/ja.2011.21 · Cited by 370 · see citing works
Ethnopharmacology and systems biology: A perfect holistic match
Verpoorte, R., Choi, Y. H., & Kim, H. K. (2005) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2005.05.033 · Cited by 296 · see citing works
Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians
Donia, M. S., Hathaway, B. J., Sudek, S., Haygood, M. G., Rosovitz, M. J., Ravel, J., & Schmidt, E. W. (2006) · Nature Chemical Biology · doi:10.1038/nchembio829 · Cited by 261 · see citing works
Bioactivities from marine algae of the genus Gracilaria
De Almeida, C. L. F., De S. Falcão, H., De M. Lima, G. R., De A. Montenegro, C., Lira, N. S., De Athayde-Filho, P. F., Rodrigues, L. C., De Souza, M. D. F. V., Barbosa-Filho, J. M., & Batista, L. M. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12074550 · Cited by 252 · see citing works
Pharmaceutical applications of cyanobacteria—A review
Vijayakumar, S., & Menakha, M. (2015) · Journal of Acute Medicine · doi:10.1016/j.jacme.2015.02.004 · Cited by 205 · see citing works
Confronting the challenges of natural product-based antifungal discovery
Roemer, T., Xu, D., Singh, S. B., Parish, C. A., Harris, G., Wang, H., Davies, J. E., & Bills, G. F. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.01.009 · Cited by 147 · see citing works
Divino da Rocha, M., Pereira Dias Viegas, F., Cristina Campos, H., Carolina Nicastro, P., Calve Fossaluzza, P., Alberto Manssour Fraga, C., J. Barreiro, E., & Viegas, C. (2011) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152711794480429 · Cited by 126 · see citing works
Ma, D., Zou, B., Cai, G., Hu, X., & Liu, J. O. (2006) · Chemistry – A European Journal · doi:10.1002/chem.200600599 · Cited by 99 · see citing works
Hollands, A., Corriden, R., Gysler, G., Dahesh, S., Olson, J., Raza Ali, S., Kunkel, M. T., Lin, A. E., Forli, S., Newton, A. C., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.695866 · Cited by 73 · see citing works
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Javed, F., Qadir, M. I., Janbaz, K. H., & Ali, M. (2011) · Critical Reviews in Microbiology · doi:10.3109/1040841x.2011.576234 · Cited by 72 · see citing works
Ethnomedicinal uses of plants for the treatment of malaria in Soon Valley, Khushab, Pakistan
Shah, A., & Rahim, S. (2017) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2017.02.005 · Cited by 61 · see citing works
Pane, G., Cacciola, G., Giacco, E., Mariottini, G., & Coppo, E. (2015) · Marine Drugs · doi:10.3390/md13106440 · Cited by 56 · see citing works
Formulation and Evaluation of Antifungal Soap Using Latex of Calotropis gigantea L.
Kharnare, R. M., Bairagi, V. A., Chavhan, R. B., Shivde, T. S., Khalane, S. M., & Lengare, S. R. (2026) · International Journal of Research in Engineering, Science and Management · doi:10.65138/ijresm.v9i5.3451
- Authors
- Newman, D. J., Cragg, G. M., & Snader, K. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Newman, David J.
- Venue
- Journal of Natural Products
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-06-12
- Volume
- 66
- Issue
- 7
- Pages
- 1022-1037
- ISSN
- 0163-3864 (ISSN-L)
- 1520-6025
- OpenAlex
- W2162331245
- Cited by
- 3,082
- References
- 45
- Citations by year
- 2026: 46 · 2025: 45 · 2024: 80 · 2023: 113 · 2022: 135 · 2021: 124 · 2020: 133 · 2019: 137 · 2018: 133 · 2017: 135 · 2016: 134 · 2015: 181 · 2014: 176 · 2013: 200 · 2012: 206
- FWCI
- 11.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Natural Products (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
- Keywords
- natural products, drug discovery, new chemical entities, anticancer agents, antihypertensive drugs, antimigraine drugs, serotonin derivatives, combinatorial chemistry, structural optimization, drug approval
- MeSH terms
- Biological Products, Pharmacology, Research, Molecular Structure, Drug Approval, Combinatorial Chemistry Techniques, History, 20th Century, History, 21st Century
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