New horizons for old drugs and drug leads.

There is mounting urgency to find new drugs for the treatment of serious infectious diseases and cancer that are rapidly developing resistance to previously effective drugs. One approach to addressing this need is through drug repurposing, which refers to the discovery of new useful activities for "old" clinically used drugs through screening them against relevant disease targets. A large number of potential drug that, for various reasons, have failed to advance to clinical and commercial use can be added to the candidates available for such purposes. The application of new techniques and methodology developed through the impressive progress made in multidisciplinary, natural product-related research in recent years should aid substantially in expediting the discovery and development process. This review briefly outlines some of these developments as applied to a number of selected natural product examples, which may also include advances in chemical synthesis of derivatives with extended biological activities.

[1]  J. Rhim,et al.  HPMA copolymer-based combination therapy toxic to both prostate cancer stem/progenitor cells and differentiated cells induces durable anti-tumor effects. , 2013, Journal of Controlled Release.

[2]  Sahdeo Prasad,et al.  Cancer drug discovery by repurposing: teaching new tricks to old dogs. , 2013, Trends in pharmacological sciences.

[3]  Xiaohu Zhang,et al.  Cyclopamine, a naturally occurring alkaloid, and its analogues may find wide applications in cancer therapy. , 2013, Current topics in medicinal chemistry.

[4]  Noel Southall,et al.  Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens , 2013, PloS one.

[5]  Melvin J. Yu,et al.  From micrograms to grams: scale-up synthesis of eribulin mesylate. , 2013, Natural product reports.

[6]  J. Lambert Drug‐conjugated antibodies for the treatment of cancer , 2013, British journal of clinical pharmacology.

[7]  G. Berg,et al.  A study of the bacterial community in the root system of the maytansine containing plant Putterlickia verrucosa. , 2013, Phytochemistry.

[8]  F. Reyes,et al.  Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds. , 2013, Journal of the American Chemical Society.

[9]  David Cavalla,et al.  Predictive methods in drug repurposing: gold mine or just a bigger haystack? , 2013, Drug discovery today.

[10]  David J Newman,et al.  Natural products: a continuing source of novel drug leads. , 2013, Biochimica et biophysica acta.

[11]  H. Abboud Synthetic oleanane triterpenoids: magic bullets or not? , 2013, Kidney international.

[12]  C. Rudin,et al.  Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors , 2013, Clinical Cancer Research.

[13]  J. McMurray,et al.  Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON) , 2013, American Journal of Nephrology.

[14]  Li Huang,et al.  New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. , 2013, Journal of medicinal chemistry.

[15]  L. Costa-Lotufo,et al.  Overview of the therapeutic potential of piplartine (piperlongumine). , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[16]  Herbert Waldmann,et al.  Biology‐Oriented Synthesis of a Tetrahydroisoquinoline‐Based Compound Collection Targeting Microtubule Polymerization , 2013, Chembiochem : a European journal of chemical biology.

[17]  S. Linder,et al.  Piperlongumine induces inhibition of the ubiquitin-proteasome system in cancer cells. , 2013, Biochemical and biophysical research communications.

[18]  Christine J. Martin,et al.  Structure guided design of improved anti-proliferative rapalogs through biosynthetic medicinal chemistry , 2013 .

[19]  J. Cummings,et al.  A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents , 2013, Dementia and Geriatric Cognitive Disorders.

[20]  R. Uzzo,et al.  Piperlongumine induces rapid depletion of the androgen receptor in human prostate cancer cells , 2013, The Prostate.

[21]  U. Tatu,et al.  Heat shock protein 90 inhibitors as broad spectrum anti-infectives. , 2012, Current pharmaceutical design.

[22]  D. Budman,et al.  Trastuzumab-DM1: A Clinical Update of the Novel Antibody-Drug Conjugate for HER2-Overexpressing Breast Cancer , 2012, Molecular medicine.

[23]  F. Koehn Natural Products and Cancer Drug Discovery , 2013 .

[24]  Christine J. Martin,et al.  Recombinant strains for the enhanced production of bioengineered rapalogs. , 2013, Metabolic engineering.

[25]  S. Corey,et al.  Drug repurposing in pediatrics and pediatric hematology oncology. , 2013, Drug discovery today.

[26]  R. Biggar,et al.  Breast cancer in women using digoxin: tumor characteristics and relapse risk , 2013, Breast Cancer Research.

[27]  L. Didone,et al.  A Repurposing Approach Identifies Off-Patent Drugs with Fungicidal Cryptococcal Activity, a Common Structural Chemotype, and Pharmacological Properties Relevant to the Treatment of Cryptococcosis , 2012, Eukaryotic Cell.

[28]  Leonard Katz,et al.  Genome-based bioprospecting of microbes for new therapeutics. , 2012, Current opinion in biotechnology.

[29]  B. Wilkinson,et al.  Bioengineering natural product biosynthetic pathways for therapeutic applications. , 2012, Current opinion in biotechnology.

[30]  Young-Soo Hong,et al.  New geldanamycin analogs from Streptomyces hygroscopicus. , 2012, Journal of microbiology and biotechnology.

[31]  S. Cole,et al.  Towards a new tuberculosis drug: pyridomycin – nature's isoniazid , 2012, EMBO molecular medicine.

[32]  Gerard D. Wright Back to the future: a new ‘old’ lead for tuberculosis , 2012, EMBO molecular medicine.

[33]  S. Schreiber,et al.  Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs , 2012, Proceedings of the National Academy of Sciences.

[34]  Xi-shi Liu,et al.  Histone deacetylase inhibitors as therapeutics for endometriosis , 2012 .

[35]  D. Krysan,et al.  Antifungal Drug Discovery: Something Old and Something New , 2012, PLoS pathogens.

[36]  Kyle Petersen,et al.  Repurposing screens identify rifamycins as potential broad-spectrum therapy for multidrug-resistant Acinetobacter baumannii and select agent microorganisms. , 2012, Future microbiology.

[37]  R. Biggar,et al.  Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix , 2012, International journal of cancer.

[38]  Tudor I. Oprea,et al.  Drug Repurposing: Far Beyond New Targets for Old Drugs , 2012, The AAPS Journal.

[39]  R. Capon Microbial biodiscovery: back to the future. , 2012, Current topics in medicinal chemistry.

[40]  W. Childers,et al.  Targeting neurodegenerative diseases: Drug discovery in a challenging arena , 2012 .

[41]  D. Mitchison,et al.  The chemotherapy of tuberculosis: past, present and future [State of the art]. , 2012, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[42]  M. Marsden,et al.  Designed, Synthetically Accessible Bryostatin Analogues Potently Induce Activation of Latent HIV Reservoirs in vitro , 2012, Nature chemistry.

[43]  Jeffrey Aubé,et al.  Drug repurposing and the medicinal chemist. , 2012, ACS medicinal chemistry letters.

[44]  J. O’Grady,et al.  Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs. , 2012, The Journal of infectious diseases.

[45]  Cerasela Zoica Dinu,et al.  Digitoxin and its analogs as novel cancer therapeutics , 2012, Experimental Hematology & Oncology.

[46]  C. Khosla,et al.  Combinatorial biosynthesis of polyketides--a perspective. , 2012, Current opinion in chemical biology.

[47]  B. Gicquel,et al.  Mycobacterium abscessus: a new antibiotic nightmare. , 2012, The Journal of antimicrobial chemotherapy.

[48]  Neil Swanson,et al.  Ingenol mebutate gel for actinic keratosis. , 2012, The New England journal of medicine.

[49]  David J Newman,et al.  Natural products as sources of new drugs over the 30 years from 1981 to 2010. , 2012, Journal of natural products.

[50]  J. Kopeček,et al.  Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate cancer stem cells. , 2012, Biomaterials.

[51]  J. Scheuermann,et al.  A traceless vascular-targeting antibody-drug conjugate for cancer therapy. , 2012, Angewandte Chemie.

[52]  D. Felsher,et al.  “Picolog,” a Synthetically-Available Bryostatin Analog, Inhibits Growth of MYC-Induced Lymphoma In Vivo , 2012, Oncotarget.

[53]  P. Wender,et al.  Function Oriented Synthesis: Preparation and Initial Biological Evaluation of New A-Ring-Modified Bryologs. , 2011, Tetrahedron.

[54]  R. Santaolalla,et al.  TLR signaling: a link between gut microflora, colorectal inflammation and tumorigenesis , 2011 .

[55]  Elizabeth I. Parkinson,et al.  Runaway ROS as a Selective Anticancer Strategy , 2011, ChemMedChem.

[56]  A. Ricart Antibody-Drug Conjugates of Calicheamicin Derivative: Gemtuzumab Ozogamicin and Inotuzumab Ozogamicin , 2011, Clinical Cancer Research.

[57]  B. Teicher,et al.  Antibody Conjugate Therapeutics: Challenges and Potential , 2011, Clinical Cancer Research.

[58]  A. Younes,et al.  Brentuximab Vedotin (SGN-35) , 2011, Clinical Cancer Research.

[59]  R. Lutz,et al.  SAR3419: An Anti-CD19-Maytansinoid Immunoconjugate for the Treatment of B-Cell Malignancies , 2011, Clinical Cancer Research.

[60]  M. Sliwkowski,et al.  Trastuzumab Emtansine: A Unique Antibody-Drug Conjugate in Development for Human Epidermal Growth Factor Receptor 2–Positive Cancer , 2011, Clinical Cancer Research.

[61]  K. Hale,et al.  Total synthesis of bryostatin 1: a short route. , 2011, Angewandte Chemie.

[62]  D. Livermore Discovery research: the scientific challenge of finding new antibiotics. , 2011, The Journal of antimicrobial chemotherapy.

[63]  Philip Raskin,et al.  Bardoxolone methyl and kidney function in CKD with type 2 diabetes. , 2011, The New England journal of medicine.

[64]  T. Golub,et al.  Selective killing of cancer cells with a small molecule targeting stress response to ROS , 2011, Nature.

[65]  S. Chopra,et al.  Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae. , 2011, The Journal of antimicrobial chemotherapy.

[66]  Lavonne Patton,et al.  New sources of drugs for hematologic malignancies. , 2011, Blood.

[67]  Z. Deng,et al.  Identification and characterization of the pyridomycin biosynthetic gene cluster of Streptomyces pyridomyceticus NRRL B-2517. , 2011, The Journal of biological chemistry.

[68]  Young-Soo Hong,et al.  New non-quinone geldanamycin analogs from genetically engineered Streptomyces hygroscopicus , 2011, The Journal of Antibiotics.

[69]  Edward Giovannucci,et al.  A novel two-stage, transdisciplinary study identifies digoxin as a possible drug for prostate cancer treatment. , 2011, Cancer discovery.

[70]  Francis S. Collins,et al.  Mining for therapeutic gold , 2011, Nature Reviews Drug Discovery.

[71]  Sean Ekins,et al.  Finding Promiscuous Old Drugs for New Uses , 2011, Pharmaceutical Research.

[72]  B. Grimberg,et al.  Expanding the Antimalarial Drug Arsenal—Now, But How? , 2011, Pharmaceuticals.

[73]  D. Warnock,et al.  Effect of Bardoxolone Methyl on Kidney Function in Patients with T2D and Stage 3b–4 CKD , 2011, American Journal of Nephrology.

[74]  P. Wender,et al.  Translating Nature's Library: The Bryostatins and Function-Oriented Synthesis. , 2011, Israel journal of chemistry.

[75]  F. Kelleher Hedgehog signaling and therapeutics in pancreatic cancer. , 2011, Carcinogenesis.

[76]  Vishal A. Verma,et al.  Design, synthesis, and evaluation of potent bryostatin analogs that modulate PKC translocation selectivity , 2011, Proceedings of the National Academy of Sciences.

[77]  Melvin J. Yu,et al.  Novel second generation analogs of eribulin. Part III: Blood-brain barrier permeability and in vivo activity in a brain tumor model. , 2011, Bioorganic & medicinal chemistry letters.

[78]  Melvin J. Yu,et al.  Novel second generation analogs of eribulin. Part I: Compounds containing a lipophilic C32 side chain overcome P-glycoprotein susceptibility. , 2011, Bioorganic & medicinal chemistry letters.

[79]  Melvin J. Yu,et al.  Novel second generation analogs of eribulin. Part II: Orally available and active against resistant tumors in vivo. , 2011, Bioorganic & medicinal chemistry letters.

[80]  A. Gould,et al.  Targeting the hedgehog pathway: the development of cyclopamine and the development of anti-cancer drugs targeting the hedgehog pathway. , 2011, Mini reviews in medicinal chemistry.

[81]  D. Nielsen,et al.  Trastuzumab emtansine, tumor-activated prodrug (TAP) immunoconjungate, oncolytic , 2011 .

[82]  G. Feldmann,et al.  Agents targeting the Hedgehog pathway for pancreatic cancer treatment. , 2010, Current opinion in investigational drugs.

[83]  J. Switzer,et al.  Minocycline to Improve Neurologic Outcome in Stroke (MINOS): A Dose-Finding Study , 2010, Stroke.

[84]  D. Newman,et al.  Plant Natural Products in Anticancer Drug Discovery , 2010 .

[85]  Bethan Hughes Antibody–drug conjugates for cancer: poised to deliver? , 2010, Nature Reviews Drug Discovery.

[86]  Gert Storm,et al.  Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release , 2010, Pharmaceutical Research.

[87]  Alexey Lugovskoy,et al.  Design of next-generation protein therapeutics. , 2010, Current opinion in chemical biology.

[88]  Stephen C Alley,et al.  Antibody-drug conjugates: targeted drug delivery for cancer. , 2010, Current opinion in chemical biology.

[89]  Yeo Joon Yoon,et al.  Biosynthesis of rapamycin and its regulation: past achievements and recent progress , 2010, The Journal of Antibiotics.

[90]  M. Nagarkatti,et al.  Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner , 2010, PloS one.

[91]  A. Giannis,et al.  Cyclopamine and hedgehog signaling: chemistry, biology, medical perspectives. , 2010, Angewandte Chemie.

[92]  Clay S. Bennett,et al.  Design, synthesis, and biological evaluation of EF- and ABEF- analogues of (+)-spongistatin 1. , 2010, Organic letters.

[93]  K. Hale,et al.  New approaches to the total synthesis of the bryostatin antitumor macrolides. , 2010, Chemistry, an Asian journal.

[94]  Jan Albert,et al.  Can the further clinical development of bevirimat be justified? , 2010, AIDS.

[95]  Michael A Fischbach,et al.  Natural products version 2.0: connecting genes to molecules. , 2010, Journal of the American Chemical Society.

[96]  J. Lambert Antibody-maytansinoid conjugates: A new strategy for the treatment of cancer , 2010, Drugs of the Future.

[97]  Teicher Ba Antibody-drug conjugate targets. , 2009 .

[98]  David J Newman,et al.  Natural product scaffolds as leads to drugs. , 2009, Future medicinal chemistry.

[99]  Keduo Qian,et al.  Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents. , 2009, Natural product reports.

[100]  R. Gebhardt,et al.  From teratogens to potential therapeutics: natural inhibitors of the Hedgehog signaling network come of age. , 2009, Planta medica.

[101]  Arsène Burny,et al.  Synergistic Activation of HIV-1 Expression by Deacetylase Inhibitors and Prostratin: Implications for Treatment of Latent Infection , 2009, PloS one.

[102]  Jeanne A. Ferguson,et al.  Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926). , 2009, Journal of medicinal chemistry.

[103]  P. Senter Potent antibody drug conjugates for cancer therapy. , 2009, Current opinion in chemical biology.

[104]  Li Huang,et al.  Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents. , 2009, Journal of medicinal chemistry.

[105]  D. Newman,et al.  Impact of natural products on developing new anti-cancer agents. , 2009, Chemical reviews.

[106]  T. Triche,et al.  Characterization of NVX‐207, a novel betulinic acid‐derived anti‐cancer compound , 2009, European journal of clinical investigation.

[107]  E. Graziani,et al.  Recent advances in the chemistry, biosynthesis and pharmacology of rapamycin analogs. , 2009, Natural product reports.

[108]  James T. Elder,et al.  Lack of evidence for activation of the hedgehog pathway in psoriasis. , 2009, The Journal of investigative dermatology.

[109]  J. McAlpine Advances in the understanding and use of the genomic base of microbial secondary metabolite biosynthesis for the discovery of new natural products. , 2009, Journal of natural products.

[110]  S. Maffioli,et al.  Bacterial RNA polymerase inhibitors: an organized overview of their structure, derivatives, biological activity and current clinical development status. , 2009, Current medicinal chemistry.

[111]  Hugh S. Taylor,et al.  Experimental Murine Endometriosis Induces DNA Methylation and Altered Gene Expression in Eutopic Endometrium1 , 2009, Biology of reproduction.

[112]  T. Molinski,et al.  Drug development from marine natural products , 2009, Nature Reviews Drug Discovery.

[113]  Guangbin Dong,et al.  Total synthesis of bryostatin 16 using atom-economical and chemoselective approaches , 2008, Nature.

[114]  T. Knobloch,et al.  Iconography : The chemistry and biology of the maytansinoid antitumor agents , 2008 .

[115]  Mohammad Nur-E-Alam,et al.  Optimizing natural products by biosynthetic engineering: discovery of nonquinone Hsp90 inhibitors. , 2008, Journal of medicinal chemistry.

[116]  P. Wender,et al.  Practical Synthesis of Prostratin, DPP, and Their Analogs, Adjuvant Leads Against Latent HIV , 2008, Science.

[117]  D. Alkon,et al.  Analysis of long-term cognitive-enhancing effects of bryostatin-1 on the rabbit (Oryctolagus cuniculus) nictitating membrane response , 2008, Behavioural pharmacology.

[118]  J. Lord,et al.  Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling in cancer cells , 2008, Molecular Cancer Therapeutics.

[119]  Christine J. Martin,et al.  Molecular characterization of macbecin as an Hsp90 inhibitor. , 2008, Journal of medicinal chemistry.

[120]  A. Maitra,et al.  Targeted inhibition of hedgehog signaling by cyclopamine prodrugs for advanced prostate cancer. , 2008, Bioorganic & medicinal chemistry.

[121]  Young‐Tae Chang,et al.  Synthesis and anticancer activity studies of cyclopamine derivatives. , 2008, Bioorganic & medicinal chemistry letters.

[122]  A. Awada,et al.  Novel cytotoxic drugs: old challenges, new solutions. , 2008, Cancer treatment reviews.

[123]  D. Rubinsztein,et al.  A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin. , 2008, Human molecular genetics.

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

[125]  S. Wetzel,et al.  Biology-inspired synthesis of compound libraries , 2008, Cellular and Molecular Life Sciences.

[126]  Keduo Qian,et al.  Anti-AIDS agents 73: structure-activity relationship study and asymmetric synthesis of 3-O-monomethylsuccinyl-betulinic acid derivatives. , 2007, Bioorganic & medicinal chemistry letters.

[127]  M. Sporn,et al.  The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent antiangiogenic agent , 2007, Molecular Cancer Therapeutics.

[128]  D. Baker,et al.  The value of natural products to future pharmaceutical discovery. , 2007, Natural product reports.

[129]  M. Boaz,et al.  MINOCYCLINE TREATMENT IN ACUTE STROKE : AN OPEN-LABEL, EVALUATOR-BLINDED STUDY. Authors' reply , 2008 .

[130]  M. Ratain,et al.  Rapamycin: Something Old, Something New, Sometimes Borrowed and Now Renewed , 2007, Clinical pharmacology and therapeutics.

[131]  Z. Lu,et al.  Altered expression of HOXA10 in endometriosis: potential role in decidualization. , 2007, Molecular human reproduction.

[132]  C. Iacobuzio-Donahue,et al.  Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. , 2007, Cancer research.

[133]  D. Alkon,et al.  PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer's disease. , 2007, Trends in pharmacological sciences.

[134]  J. Montaner Stroke biomarkers: can they help us to guide stroke thrombolysis? , 2006, Timely topics in medicine. Cardiovascular diseases.

[135]  D. Pompliano,et al.  Drugs for bad bugs: confronting the challenges of antibacterial discovery , 2007, Nature Reviews Drug Discovery.

[136]  Lee L. Rubin,et al.  Targeting the Hedgehog pathway in cancer , 2006, Nature Reviews Drug Discovery.

[137]  J. Weinberg,et al.  Cyclopamine: inhibiting hedgehog in the treatment of psoriasis. , 2006, Cutis.

[138]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[139]  I. Rayment,et al.  Actin-targeting natural products: structures, properties and mechanisms of action , 2006, Cellular and Molecular Life Sciences CMLS.

[140]  S. Danishefsky,et al.  Small molecule natural products in the discovery of therapeutic agents: the synthesis connection. , 2006, The Journal of organic chemistry.

[141]  James R. Porter,et al.  Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of Hsp90. , 2006, Journal of medicinal chemistry.

[142]  M. Gheorghiade,et al.  Contemporary Use of Digoxin in the Management of Cardiovascular Disorders , 2006, Circulation.

[143]  Herbert Waldmann,et al.  Charting Biological and Chemical Space: PSSC and SCONP as Guiding Principles for the Development of Compound Collections Based on Natural Product Scaffolds , 2006 .

[144]  Li Huang,et al.  Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives. , 2006, Bioorganic & medicinal chemistry.

[145]  J. Montaner Latest advances and research in stroke: Focus on diagnostic and therapeutic targets. , 2006, Drug news & perspectives.

[146]  D. Alkon,et al.  Bryostatin-1: pharmacology and therapeutic potential as a CNS drug. , 2006, CNS drug reviews.

[147]  Cragg Gm,et al.  Natural products from marine invertebrates and microbes as modulators of antitumor targets. , 2006 .

[148]  F. Khanim,et al.  PEP005, a selective small-molecule activator of protein kinase C, has potent antileukemic activity mediated via the delta isoform of PKC. , 2005, Blood.

[149]  David E. Martin,et al.  The discovery of a class of novel HIV-1 maturation inhibitors and their potential in the therapy of HIV , 2005, Expert opinion on investigational drugs.

[150]  M. Sporn,et al.  Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action. , 2005, Bioorganic & medicinal chemistry letters.

[151]  Perumal Yogeeswari,et al.  Betulinic acid and its derivatives: a review on their biological properties. , 2005, Current medicinal chemistry.

[152]  Herbert Waldmann,et al.  Compound library development guided by protein structure similarity clustering and natural product structure. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[153]  A. Demain Pickles, pectin, and penicillin. , 2004, Annual review of microbiology.

[154]  D. Alkon,et al.  Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

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

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

[157]  M. Konopleva,et al.  Growth-inhibitory effect of a novel synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, on ovarian carcinoma cell lines not dependent on peroxisome proliferator-activated receptor-γ expression , 2004 .

[158]  David J Newman,et al.  A tale of two tumor targets: topoisomerase I and tubulin. The Wall and Wani contribution to cancer chemotherapy. , 2004, Journal of natural products.

[159]  Xin-Yun Huang,et al.  Discovery of potent cell migration inhibitors through total synthesis: lessons from structure-activity studies of (+)-migrastatin. , 2004, Journal of the American Chemical Society.

[160]  R. Cichewicz,et al.  Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection , 2004, Medicinal research reviews.

[161]  Á. Ravelo,et al.  Recent studies on natural products as anticancer agents. , 2004, Current topics in medicinal chemistry.

[162]  L. Meijer Le cycle de division cellulaire et sa régulation , 2006 .

[163]  P. Wender,et al.  A new synthetic approach to the C ring of known as well as novel bryostatin analogues. , 2003, Organic letters.

[164]  Stuart L Schreiber,et al.  Discovery of an inhibitor of a transcription factor using small molecule microarrays and diversity-oriented synthesis. , 2003, Journal of the American Chemical Society.

[165]  A. Färnert,et al.  Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports , 2003, BMJ : British Medical Journal.

[166]  Gabriel Fenteany,et al.  Small-molecule inhibitors of actin dynamics and cell motility. , 2003, Current topics in medicinal chemistry.

[167]  A. Mayweg,et al.  A concise, selective synthesis of the polyketide spacer domain of a potent bryostatin analogue. , 2003, Organic letters.

[168]  K. Yeung,et al.  Actin-binding marine macrolides: total synthesis and biological importance. , 2002, Angewandte Chemie.

[169]  Herbert Waldmann,et al.  Natural product guided compound library development. , 2002, Current medicinal chemistry.

[170]  David J Newman,et al.  Natural products and derivatives as leads to cell cycle pathway targets in cancer chemotherapy. , 2002, Current cancer drug targets.

[171]  Jussi Taipale,et al.  Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. , 2002, Genes & development.

[172]  P. Wender,et al.  The practical synthesis of a novel and highly potent analogue of bryostatin. , 2002, Journal of the American Chemical Society.

[173]  Herbert Waldmann,et al.  From protein domains to drug candidates-natural products as guiding principles in the design and synthesis of compound libraries. , 2002, Angewandte Chemie.

[174]  Y. Korin,et al.  Effects of Prostratin on T-Cell Activation and Human Immunodeficiency Virus Latency , 2002, Journal of Virology.

[175]  Mark Frigerio,et al.  The chemistry and biology of the bryostatin antitumour macrolides. , 2002, Natural product reports.

[176]  H. Waldmann,et al.  Natural products are biologically validated starting points in structural space for compound library development: solid-phase synthesis of dysidiolide-derived phosphatase inhibitors. , 2002, Angewandte Chemie.

[177]  P. Clemons,et al.  A one-bead, one-stock solution approach to chemical genetics: part 2. , 2001, Chemistry & biology.

[178]  John A. Tallarico,et al.  A one-bead, one-stock solution approach to chemical genetics: part 1. , 2001, Chemistry & biology.

[179]  M. Boyd,et al.  Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. , 2001, Blood.

[180]  F. Uckun,et al.  Spongistatins as tubulin targeting agents. , 2001, Current pharmaceutical design.

[181]  Y. Feng,et al.  Use of biomimetic diversity-oriented synthesis to discover galanthamine-like molecules with biological properties beyond those of the natural product. , 2001, Journal of the American Chemical Society.

[182]  J. Pezzuto,et al.  Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocytic naeval cells: evidence for a potential role as a chemopreventive agent , 2001, Melanoma research.

[183]  S. Telford,et al.  Atovaquone and azithromycin for the treatment of babesiosis. , 2000, The New England journal of medicine.

[184]  Paul A. Wender,et al.  Synthesis and biological evaluation of a new class of bryostatin analogues: the role of the C20 substituent in protein kinase C binding , 2000 .

[185]  M. Wills,et al.  Chemistry and clinical biology of the bryostatins. , 2000, Bioorganic & medicinal chemistry.

[186]  C. Farquhar Extracts from the "clinical evidence". Endometriosis. , 2000, BMJ.

[187]  P. Wender,et al.  Synthesis and Biological Evaluation of Bryostatin Analogues: The Role of the A-Ring. , 2000 .

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

[189]  K. Hinkle,et al.  The rational design of potential chemotherapeutic agents: Synthesis of bryostatin analogues , 1999, Medicinal research reviews.

[190]  S. Looareesuwan,et al.  Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. , 1999, The American journal of tropical medicine and hygiene.

[191]  K. Hinkle,et al.  Synthesis and biological evaluation of fully synthetic bryostatin analogues , 1998 .

[192]  P. Wender,et al.  The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[193]  Makoto Shiozaki,et al.  Synthesis of the First Members of a New Class of Biologically Active Bryostatin Analogues , 1998 .

[194]  Neal Rosen,et al.  Crystal Structure of an Hsp90–Geldanamycin Complex: Targeting of a Protein Chaperone by an Antitumor Agent , 1997, Cell.

[195]  G. Pettit Progress in the discovery of biosynthetic anticancer drugs. , 1996, Journal of natural products.

[196]  I. Paterson,et al.  Total Synthesis of Bioactive Marine Macrolides , 1995 .

[197]  S. Pillemer,et al.  Minocycline in Rheumatoid Arthritis: A 48-Week, Double-Blind, Placebo-Controlled Trial , 1995, Annals of Internal Medicine.

[198]  L. Neckers,et al.  Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[199]  S. Follansbee,et al.  Oral Atovaquone Compared with Intravenous Pentamidine for Pneumocystis carinii Pneumonia in Patients with AIDS , 1994, Annals of Internal Medicine.

[200]  Stuart L. Schreiber,et al.  A mammalian protein targeted by G1-arresting rapamycin–receptor complex , 1994, Nature.

[201]  D. Marmé,et al.  Gö 6976, a selective inhibitor of protein kinase C, is a potent antagonist of human immunodeficiency virus 1 induction from latent/low-level-producing reservoir cells in vitro. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[202]  Craig J. Forsyth,et al.  Total synthesis of halichondrin B and norhalichondrin B , 1992 .

[203]  J. Heitman,et al.  Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast , 1991, Science.

[204]  A. Fauci,et al.  Direct and cytokine-mediated activation of protein kinase C induces human immunodeficiency virus expression in chronically infected promonocytic cells , 1990, Journal of virology.

[205]  K. Koehler,et al.  Modeling of the bryostatins to the phorbol ester pharmacophore on protein kinase C. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[206]  S. Amano,et al.  Dactylosporangium fulvum sp. nov. , 1986 .

[207]  T. Hickey,et al.  Irritant contact dermatitis in humans from phorbol and related esters. , 1981, Toxicon : official journal of the International Society on Toxinology.

[208]  S. Sehgal,et al.  Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation. , 1978, The Journal of antibiotics.

[209]  D. Weedon,et al.  Home treatment of basal cell carcinoma. , 1976, The Medical journal of Australia.

[210]  S. Sehgal,et al.  Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization.:II. FERMENTATION, ISOLATION AND CHARACTERIZATION , 1975 .

[211]  S. Sehgal,et al.  Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. , 1975, The Journal of antibiotics.

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

[213]  V. Arioli,et al.  Rifamycins. XLI. A new class of active semisynthetic rifamycins. N-substituted aminomethyl derivatives of rifamycin SV 2. , 1965, Journal of medicinal chemistry.

[214]  G. Carraz,et al.  [Pharmacodynamic properties of N-dipropylacetic acid]. , 1963, Therapie.

[215]  CYRIL M. HARRIS,et al.  The New York Academy of Sciences , 1881, Nature.

[216]  H. Umezawa,et al.  A new antibiotic, pyridomycin. , 1953, The Journal of antibiotics.