Drug discovery from natural sources

Organic compounds from terrestrial and marine organisms have extensive past and present use in the treatment of many diseases and serve as compounds of interest both in their natural form and as templates for synthetic modification. Over 20 new drugs launched on the market between 2000 and 2005, originating from terrestrial plants, terrestrial microorganisms, marine organisms, and terrestrial vertebrates and invertebrates, are described. These approved substances, representative of very wide chemical diversity, together with several other natural products or their analogs undergoing clinical trials, continue to demonstrate the importance of compounds from natural sources in modern drug discovery efforts.

[1]  F. Arcamone,et al.  Experimental studies on distamycin A--a new antibiotic with cytotoxic activity. , 1962, Cancer chemotherapy reports.

[2]  O. Tanaka,et al.  On genuine sapogenin of ginseng , 1963 .

[3]  T. Mcmorris,et al.  FUNGAL METABOLITES. THE STRUCTURES OF THE NOVEL SESQUITERPENOIDS ILLUDIN-S AND -M. , 1965, Journal of the American Chemical Society.

[4]  K. Au,et al.  A new antibiotic? , 1969, Biochemical pharmacology.

[5]  D. Weisleder,et al.  Structures of harringtonine, isoharringtonine, and homoharringtonine. , 1970, Tetrahedron letters.

[6]  C. Deboer,et al.  Geldanamycin, a new antibiotic. , 1970, The Journal of antibiotics.

[7]  K. Rinehart,et al.  Geldanamycin. I. Structure assignment. , 1970, Journal of the American Chemical Society.

[8]  Tadashi. Sasaki,et al.  Chrysanthemic acid. V. Thermal and photo [3,3]sigmatropic rearrangements in the cis-2,2-dimethyl-3-isobutenylcyclopropyl isocyanate-3,6-dihydro-3,3,6,6-tetramethyl-2H-azepin-2-one system , 1970 .

[9]  K. Nagashima,et al.  A new antifungal antibiotic, trichostatin. , 1976, The Journal of antibiotics.

[10]  Kenneth B. Tomer,et al.  The isolation and structure of a remarkable marine animal antineoplastic constituent: dolastatin 10 , 1987 .

[11]  M. Siegel,et al.  Calichemicins, a novel family of antitumor antibiotics. 1. Chemistry and partial structure of calichemicin .gamma.1I , 1987 .

[12]  R. Cerny,et al.  Isolation and Structure of the Cytostatic Linear Depsipeptide Dolastatin 15 , 1989 .

[13]  J. Veitch,et al.  Biosynthesis of elsamicin A, a novel antitumor antibiotic. , 1989, Journal of natural products.

[14]  J. Raufman,et al.  Exendin-4, a new peptide from Heloderma suspectum venom, potentiates cholecystokinin-induced amylase release from rat pancreatic acini , 1992, Regulatory Peptides.

[15]  J. Forrest,et al.  Squalamine: an aminosterol antibiotic from the shark. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[16]  A. Kinghorn,et al.  The discovery of drugs from higher plants. , 1994, Biotechnology.

[17]  T. Natori,et al.  Agelasphins, novel antitumor and immunostimulatory cerebrosides from the marine sponge Agelas mauritianus , 1994 .

[18]  T. Mcmorris,et al.  (Hydroxymethyl)acylfulvene: an illudin derivative with superior antitumor properties. , 1996, Journal of natural products.

[19]  P. Dewick,et al.  Medicinal Natural Products: A Biosynthetic Approach , 1997 .

[20]  T. Eggelte,et al.  Artemisinin drugs in the treatment of malaria: from medicinal herb to registered medication. , 1999, Trends in pharmacological sciences.

[21]  S. Noble,et al.  Mycophenolate mofetil: a review of its use in the management of solid organ transplantation. , 1999, BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy.

[22]  M. Ogawa Novel anticancer drugs in Japan , 1999, Journal of Cancer Research and Clinical Oncology.

[23]  K. Fukasawa,et al.  Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I. , 1999, Cancer research.

[24]  J. Ávila,et al.  The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. , 2000, Cancer letters.

[25]  D J Newman,et al.  The influence of natural products upon drug discovery. , 2000, Natural product reports.

[26]  P. Jensen,et al.  Marine Microorganisms and Drug Discovery: Current Status and Future Potential , 2000 .

[27]  K. Rinehart,et al.  Antitumor compounds from tunicates , 2000, Medicinal research reviews.

[28]  D. Fabbro,et al.  Differential p53-dependent mechanism of radiosensitization in vitro and in vivo by the protein kinase C-specific inhibitor PKC412. , 2001, Cancer research.

[29]  B. Cheson,et al.  Homoharringtonine: history, current research, and future direction. , 2001, Cancer.

[30]  N. Farnsworth,et al.  The value of plants used in traditional medicine for drug discovery. , 2001, Environmental health perspectives.

[31]  S. Eksborg,et al.  Pharmacokinetics and pharmacodynamics of NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione) and mesotrione, inhibitors of 4-hydroxyphenyl pyruvate dioxygenase (HPPD) following a single dose to healthy male volunteers. , 2001, British journal of clinical pharmacology.

[32]  D. C. Holt,et al.  Mesotrione: a new selective herbicide for use in maize. , 2001, Pest management science.

[33]  J. Sleeman Biodiversity and Human Health , 2009 .

[34]  R. Capon Marine Bioprospecting − Trawling for Treasure and Pleasure , 2001 .

[35]  A. Gales,et al.  Emerging strategies in infectious diseases: new carbapenem and trinem antibacterial agents. , 2001, Drugs.

[36]  B. Cheson,et al.  Homoharringtonine , 2001, Cancer.

[37]  S. Douthwaite,et al.  The ketolides: a critical review. , 2002, Drugs.

[38]  T. Gladwell Bivalirudin: a direct thrombin inhibitor. , 2002, Clinical therapeutics.

[39]  S. Forenza,et al.  Discovery of antitumor indolocarbazoles: rebeccamycin, NSC 655649, and fluoroindolocarbazoles. , 2002, Current medicinal chemistry. Anti-cancer agents.

[40]  S. Bates,et al.  Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[41]  R. Sellers,et al.  Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[42]  M. Broggini,et al.  Brostallicin, a novel anticancer agent whose activity is enhanced upon binding to glutathione. , 2002, Cancer research.

[43]  P. Finn,et al.  Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. , 2003, Molecular cancer therapeutics.

[44]  N. Perry,et al.  Plants with traditional uses and activities, relevant to the management of Alzheimer's disease and other cognitive disorders , 2003, Phytotherapy research : PTR.

[45]  Jeffrey W. Clark,et al.  Phase I clinical trial and pharmacokinetic study of the spicamycin analog KRN5500 administered as a 1-hour intravenous infusion for five consecutive days to patients with refractory solid tumors. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[46]  Burkhard Haefner,et al.  Drugs from the deep: marine natural products as drug candidates. , 2003, Drug discovery today.

[47]  Jeffrey W. Clark,et al.  Phase I Clinical Trial and Pharmacokinetic Study of the Spicamycin Analog KRN 5500 Administered as a 1-Hour Intravenous Infusion for Five Consecutive Days to Patients with Refractory Solid Tumors , 2003 .

[48]  D. Figgitt,et al.  Caspofungin , 2012, Drugs.

[49]  D. Braguer,et al.  Suppression of microtubule dynamics by discodermolide by a novel mechanism is associated with mitotic arrest and inhibition of tumor cell proliferation. , 2003, Molecular cancer therapeutics.

[50]  Y. Suárez,et al.  Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells. , 2003, Molecular cancer therapeutics.

[51]  A. Tolcher,et al.  A Phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[52]  A. Gupta,et al.  Pimecrolimus: A review , 2003, Journal of the European Academy of Dermatology and Venereology : JEADV.

[53]  A. Ravaud,et al.  Phase II study of LU 103793 (dolastatin analogue) in patients with metastatic breast cancer. , 2003, European journal of cancer.

[54]  James B. Mitchell,et al.  Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. , 2003, Cancer research.

[55]  David J Newman,et al.  Natural products as sources of new drugs over the period 1981-2002. , 2003, Journal of natural products.

[56]  J. Mann,et al.  Combretastatins: from natural products to drug discovery. , 2003, Natural product reports.

[57]  A. Husband,et al.  Phenoxodiol, a novel isoflavone derivative, inhibits dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. , 2003, European journal of cancer.

[58]  P. Kosmidis,et al.  Advanced NSCLC: new cytostatic agents. , 2003, Lung cancer.

[59]  G. Forni,et al.  α-Galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Ann Thayer SCHERING-PLOUGH TO SLICE DEEPER: Troubled drug firm takes more action to cut costs and rebuild its businesses , 2003 .

[61]  Raoul Herbrecht,et al.  Caspofungin: the first representative of a new antifungal class. , 2003, The Journal of antimicrobial chemotherapy.

[62]  G. Mor,et al.  Phenoxodiol – an isoflavone analog – induces apoptosis in chemoresistant ovarian cancer cells , 2003, Oncogene.

[63]  C. Starks,et al.  Isolation and characterization of new epothilone analogues from recombinant Myxococcus xanthus fermentations. , 2003 .

[64]  J. Sloan,et al.  A Phase II Study of the Dolastatin 15 Analogue LU 103793 in the Treatment of Advanced Non–Small-Cell Lung Cancer , 2003, American journal of clinical oncology.

[65]  J. A. Ross,et al.  PG490-88, a derivative of triptolide, causes tumor regression and sensitizes tumors to chemotherapy. , 2003, Molecular cancer therapeutics.

[66]  Ann Thayer BRISTOL-MYERS TO SETTLE SUITS: Drug firm strikes deals with states and others in generics antitrust cases , 2003 .

[67]  J. Portugal Chartreusin, elsamicin A and related anti-cancer antibiotics. , 2003, Current medicinal chemistry. Anti-cancer agents.

[68]  W. Jia,et al.  Aglycone Protopanaxadiol, a ginseng saponin inhibits P-glycoprotein and sensitizes chemotherapy drugs on multidrug resistant cancer cells. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[69]  David J Newman,et al.  Marine natural products and related compounds in clinical and advanced preclinical trials. , 2004, Journal of natural products.

[70]  J. Karlowsky,et al.  The glycylcyclines: a comparative review with the tetracyclines. , 2004, Drugs.

[71]  M. Ratain,et al.  Phase I trial of orally administered CEP-701, a novel neurotrophin receptor-linked tyrosine kinase inhibitor , 2004, Investigational New Drugs.

[72]  H. Kantarjian,et al.  Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. , 2004, Blood.

[73]  P. Atadja,et al.  Selective Growth Inhibition of Tumor Cells by a Novel Histone Deacetylase Inhibitor, NVP-LAQ824 , 2004, Cancer Research.

[74]  Mark S Butler,et al.  The role of natural product chemistry in drug discovery. , 2004, Journal of natural products.

[75]  M. Broggini,et al.  Brostallicin: a new concept in minor groove DNA binder development , 2004, Anti-cancer drugs.

[76]  D. Fabbro,et al.  PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[77]  D. Figgitt,et al.  Rosuvastatin , 2004, American journal of cardiovascular drugs : drugs, devices, and other interventions.

[78]  C. West,et al.  Combretastatin A4 phosphate. , 2004, Anti-cancer drugs.

[79]  E. Sausville,et al.  7-Hydroxystaurosporine (UCN-01) Inhibition of Akt Thr308 but not Ser473 Phosphorylation , 2004, Clinical Cancer Research.

[80]  David J Newman,et al.  Advanced preclinical and clinical trials of natural products and related compounds from marine sources. , 2004, Current medicinal chemistry.

[81]  D. Ribatti,et al.  Antiangiogenic activity of aplidine, a new agent of marine origin , 2004, British Journal of Cancer.

[82]  Protein Kinase C Characterization of the Interaction of Ingenol 3-Angelate with Updated , 2004 .

[83]  E. Rubin,et al.  Epothilones: mechanism of action and biologic activity. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[84]  Gurmeet Kaur,et al.  Antiangiogenic Properties of 17-(Dimethylaminoethylamino)-17-Demethoxygeldanamycin , 2004, Clinical Cancer Research.

[85]  P. Parsons,et al.  Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. , 2004, Cancer research.

[86]  Jian Wang,et al.  ATM-dependent CHK2 Activation Induced by Anticancer Agent, Irofulven* , 2004, Journal of Biological Chemistry.

[87]  C. D. Thompson,et al.  A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthritis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[88]  Nicholas H Oberlies,et al.  Camptothecin and taxol: historic achievements in natural products research. , 2004, Journal of natural products.

[89]  T. Fojo,et al.  Cells resistant to HTI-286 do not overexpress P-glycoprotein but have reduced drug accumulation and a point mutation in alpha-tubulin. , 2004, Molecular cancer therapeutics.

[90]  D. Chaplin,et al.  Combretastatin A4 phosphate: background and current clinical status , 2004, Expert opinion on investigational drugs.

[91]  M. Heinrich,et al.  Galanthamine from snowdrop--the development of a modern drug against Alzheimer's disease from local Caucasian knowledge. , 2004, Journal of ethnopharmacology.

[92]  C. Schroeder,et al.  Development of small molecules that mimic the binding of ω-conotoxins at the N-type voltage-gated calcium channel , 2004, Molecular Diversity.

[93]  D. Deleu,et al.  Subcutaneous Apomorphine , 2004, Drugs & aging.

[94]  E. Chun,et al.  Novel inhibitors targeted to methionine aminopeptidase 2 (MetAP2) strongly inhibit the growth of cancers in xenografted nude model , 2005, International journal of cancer.

[95]  E. Vokes,et al.  Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers , 2005, Investigational New Drugs.

[96]  M. Fukuoka,et al.  Phase I/II study of amrubicin, a novel 9-aminoanthracycline, in patients with advanced non-small-cell lung cancer , 2005, Investigational New Drugs.

[97]  G. Pastores,et al.  An open-label, noncomparative study of miglustat in type I Gaucher disease: efficacy and tolerability over 24 months of treatment. , 2005, Clinical therapeutics.

[98]  M. Ledizet,et al.  Discovery and pre-clinical development of antithrombotics from hematophagous invertebrates. , 2005, Current medicinal chemistry. Cardiovascular and hematological agents.

[99]  Marcy J. Balunas,et al.  Drug discovery from medicinal plants. , 2005, Life sciences.

[100]  E. Perez,et al.  Phase II trial of dolastatin-10 in patients with advanced breast cancer , 2005, Investigational New Drugs.

[101]  G. Keating,et al.  Mycophenolate sodium delayed release: prevention of renal transplant rejection. , 2005, Drugs.

[102]  S. Samuel,et al.  Tiotropium bromide: a new long-acting bronchodilator for the treatment of chronic obstructive pulmonary disease. , 2005, Clinical therapeutics.

[103]  B. Cravatt,et al.  Protein-reactive natural products. , 2005, Angewandte Chemie.

[104]  Jieping Zhu,et al.  Synthetic studies toward ecteinascidin 743. , 2005, The Journal of organic chemistry.

[105]  Walter Sneader,et al.  Drug Discovery (The History) , 2005 .

[106]  C. Perry,et al.  Caspofungin: a review of its use in the treatment of fungal infections. , 2005, Drugs.

[107]  J. Arts,et al.  Histone Deacetylase Inhibitors: From Chromatin Remodelling to Experimental Cancer Therapeutics , 2005 .

[108]  T. Shiraga,et al.  Identification of cytochrome P450 enzymes involved in the metabolism of FK228, a potent histone deacetylase inhibitor, in human liver microsomes. , 2005, Biological & pharmaceutical bulletin.

[109]  D. Bonatto,et al.  Low cytotoxicity of ecteinascidin 743 in yeast lacking the major endonucleolytic enzymes of base and nucleotide excision repair pathways. , 2005, Biochemical pharmacology.

[110]  F. Koehn,et al.  The evolving role of natural products in drug discovery , 2005, Nature Reviews Drug Discovery.

[111]  C. Monneret Histone deacetylase inhibitors. , 2005, European journal of medicinal chemistry.

[112]  M. Jordan,et al.  The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth , 2005, Molecular Cancer Therapeutics.

[113]  T. Lynch,et al.  A phase II study of KOS-862 (epothilone D) as second-line therapy in non-small cell lung cancer , 2005 .

[114]  J. Charrow,et al.  Guidance on the use of miglustat for treating patients with type 1 Gaucher disease , 2005, American journal of hematology.

[115]  Ian Paterson,et al.  The Renaissance of Natural Products as Drug Candidates , 2005, Science.

[116]  T. Lynch,et al.  P-565 A Phase II study of KOS-862 (Epothilone D) as second-linetherapy in non-small cell lung cancer , 2005 .

[117]  G. Giaccone,et al.  Kahalalide F Induces Necrosis-Like Cell Death that Involves Depletion of ErbB3 and Inhibition of Akt Signaling , 2005, Molecular Pharmacology.

[118]  Y. Chin,et al.  The role of pharmacognosy in modern medicine and pharmacy. , 2006, Current drug targets.

[119]  M. Butler Natural products to drugs: natural product-derived compounds in clinical trials. , 2005, Natural product reports.

[120]  A. Venditti,et al.  Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. , 2008, Cancer treatment reviews.