@article {642,
	title = {Anticancer agents from unique natural products sources},
	journal = {Pharmaceutical Biology},
	volume = {41},
	year = {2003},
	note = {ISI Document Delivery No.: 877RKTimes Cited: 5Cited Reference Count: 8344th Annual Meeting of the American-Society-of-PharmacognosyJUL 12-16, 2003Chapel Hill, NCAmer Soc PharmacognosySuppl. S},
	pages = {15-38},
	type = {Proceedings Paper},
	abstract = {The National Cooperative Natural Products Drug Discovery Group (NCNPDDG) "Anticancer Agents from Unique Natural Products Sources, CA 67786" was first awarded in September 1995. The goal of the project is to discover and develop novel anticancer agents from a variety of natural products sources. The key accomplishments of this NCDDG which will be highlighted in this manuscript include: Development of tools to probe fungi for the production of novel natural products by DNA-based probes. Discovery that the majority of these fungi can produce natural products via nonribosomal peptide synthetases, polyketide synthases, or both - a much larger percentage than current culturing techniques reveal. Identification of the MDR-selective cytotoxic agent austocystin D, and use of a novel yeast deletion strain approach to help identify its molecular target(s). Identification of hemiasterlin and other naturally occurring analogs as potent antimitotic agents with excellent in vivo activity against human solid tumors in mouse models. Development of a total synthesis of hemiasterlin. The utilization of this methodology to provide the first SAR for the hemiasterlin family of antimitotic agents and to identify the synthetic analog HTI-286, which is being examined in clinical trials as an anticancer agent. To provided technology transfer, educational opportunities and compensation to countries of origin for collection and study of their natural product resources. This NCNPDDG program has provided funding to research programs at the University of the Philippines, The University of the South Pacific in the Fiji Islands, Colombo University in Sri Lanka, the Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Brazil, and the University of Papua New Guinea.},
	keywords = {ACTIVATED PROTEIN-KINASE, antitumor agents, austocystins, CYCLIN-DEPENDENT KINASES, CYTOTOXIC PEPTIDES, fungi, GROWTH-FACTOR RECEPTOR, hemiasterlins, IN-VIVO, LINKED-IMMUNOSORBENT-ASSAY, MARINE, MICROORGANISMS, MULTIDRUG-RESISTANCE, natural products, NCDDG, sponges, TRIPEPTIDE HEMIASTERLIN, TUMOR-CELL LINES, TYROSINE KINASE},
	isbn = {1388-0209},
	url = {<Go to ISI>://000225587500004},
	author = {Ireland, C. M. and Aalbersberg, W. and Andersen, R. J. and Ayral-Kaloustian, S. and Berlinck, R. G. S. and Bernan, V. and Carter, G. and Churchill, A. C. L. and Clardy, J. and Concepcion, G. P. and De Silva, E. D. and Discafani, C. and Fojo, T. and Frost, P. and Gibson, D. and Greenberger, L. M. and Greenstein, M. and Harper, M. K. and Mallon, R. and Loganzo, F. and Nunes, M. and Poruchynsky, M. S. and Zask, A.}
}
@article {671,
	title = {HTI-286, a synthetic analogue of the tripeptide hemiasterlin, is a potent antimicrotubule agent that circumvents P-glycoprotein-mediated resistance in vitro and in vivo},
	journal = {Cancer Research},
	volume = {63},
	number = {8},
	year = {2003},
	note = {ISI Document Delivery No.: 668TETimes Cited: 57Cited Reference Count: 32},
	month = {Apr},
	pages = {1838-1845},
	type = {Article},
	abstract = {Hemiasterlin is a natural product derived from marine sponges that, like other structurally diverse peptide-like molecules, binds to the Vincapeptide site in tubulin, disrupts normal microtubule dynamics, and, at stoichiometric amounts, depolymerizes microtubules. Total synthesis of hemiasterlin and its analogues has been accomplished, and optimal pharmacological features of the series have been explored. The biological profile of one analogue, HTI-286, was studied here. HTI-286 inhibited the polymerization of purified tubulin, disrupted microtubule organization in cells, and induced mitotic arrest, as well as apoptosis. HTI-286 was a potent inhibitor of proliferation (mean IC50 = 2.5 +/- 2.1 nm in 18 human tumor cell lines) and had substantially less interaction with multidrug resistance protein (P-glycoprotein) than currently used antimicrotubule agents, including paclitaxel, docetaxel, vinorelbine, or vinblastine. Resistance to HTI-286 was not detected in cells overexpressing the drug transporters MRP1 or MXR. In athymic mice implanted with human tumor xenografts, HTI-286 administered i.v. in saline inhibited the growth of numerous human tumors derived from carcinoma of the skin, breast, prostate, brain, and colon. Marked tumor regression was observed when used on established tumors that were >1 gram in size. Moreover, HTI-286 inhibited the growth of human tumor xenografts (e.g., HCT-15, DLD-1, MX-1W, and KB-8-5) where paclitaxel and vincristine were ineffective because of inherent or acquired resistance associated with P-glycoprotein. Efficacy was also achieved with p.o. administration of HTI-286. These data suggest that HTI-286 has excellent preclinical properties that may translate into superior clinical activity, as well as provide a useful synthetic reagent to probe the drug contact sites of peptide-like molecules that interact with tubulin.},
	keywords = {ADRIAMYCIN, BETA-TUBULIN, CANCER, CARCINOMA-CELLS, CYTOTOXIC PEPTIDES, DOLASTATIN ANALOG, DRUG-RESISTANCE, EXPRESSION, MECHANISMS, MULTIDRUG-RESISTANCE},
	isbn = {0008-5472},
	url = {<Go to ISI>://000182308600021},
	author = {Loganzo, F. and Discafani, C. M. and Annable, T. and Beyer, C. and Musto, S. and Hari, M. and Tan, X. Z. and Hardy, C. and Hernandez, R. and Baxter, M. and Singanallore, T. and Khafizova, G. and Poruchynsky, M. S. and Fojo, T. and Nieman, J. A. and Ayral-Kaloustian, S. and Zask, A. and Andersen, R. J. and Greenberger, L. M.}
}
@article {701,
	title = {Synthesis and antimitotic/cytotoxic activity of hemiasterlin analogues},
	journal = {Journal of Natural Products},
	volume = {66},
	number = {2},
	year = {2003},
	note = {ISI Document Delivery No.: 652JHTimes Cited: 45Cited Reference Count: 37},
	month = {Feb},
	pages = {183-199},
	type = {Article},
	abstract = {The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.},
	keywords = {(-)-HEMIASTERLIN, AGENTS, ALPHA-AMINO-ACIDS, ASYMMETRIC-SYNTHESIS, AZIDATION, CYTOTOXIC PEPTIDES, ELEUTHEROBIN, TRIPEPTIDE, TUBULIN},
	isbn = {0163-3864},
	url = {<Go to ISI>://000181375700005},
	author = {Nieman, J. A. and Coleman, J. E. and Wallace, D. J. and Piers, E. and Lim, L. Y. and Roberge, M. and Andersen, R. J.}
}
@article {4513,
	title = {New geodiamolides from the sponge Cymbastela sp collected in Papua New Guinea},
	journal = {Journal of Natural Products},
	volume = {62},
	number = {8},
	year = {1999},
	note = {ISI Document Delivery No.: 232QMTimes Cited: 19Cited Reference Count: 15},
	month = {Aug},
	pages = {1137-1141},
	type = {Article},
	abstract = {Geodiamolides J-P (11-17) and R (19), eight new cyclic depsipetides, have been isolated from the marine sponge Cymbastela sp. collected in Papua New Guinea. The serine residue in geodiamolides L-P (13-17) and R (19) has not been previously found in this family of compounds.},
	keywords = {ANTIFUNGAL ACTIVITY, CHONDROMYCES-CROCATUS MYXOBACTERIA, CYCLODEPSIPEPTIDES, CYTOTOXIC PEPTIDES, GEODIA SP, marine sponge},
	isbn = {0163-3864},
	url = {<Go to ISI>://000082381500014},
	author = {Coleman, J. E. and Van Soest, R. and Andersen, R. J.}
}
