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Welcome to Marine Natural Products Research at the University of California in Santa Cruz
Phil
Crews, Ph.D.
Principle Investigator
Dept. of
Chemistry & Biochemistry
1156
High Street Santa Cruz, CA 95064
OFFICE PHONE: 831-459-2603
LAB PHONE: 831-459-4280
FAX: 831-459-4197
crewslab@chemistry.ucsc.edu
A primary goal of Phillip Crews' marine natural products research is to understand the chemistry of tropical marine sponges. Using bioassay-guided isolation assists us in the discovery of natural products potent against human diseases such as cancer or viruses. Our search for novel active compounds incorporates elements of structure elucidation but there are other dimensions to this research, including questions in the areas of chemical ecology, marine natural products biosynthesis, and the relationship between secondary metabolite chemistry and taxonomy. Added to these interests are emerging projects which examine sponges as a source of new cultured marine microorganisms. We are also interested in examining sponges that are rich with cyanobacterial symbionts.
Whenever possible, we try to use new concise strategies to elucidate structures, including gradient 2D NMR techniques such as HMBC, HMQC, COSY, TOCSY, NOESY, and 1H-15N HMQC. Utilization of new NMR hardware, 3mm probes and advanced NMR microtubes, nanoprobe, micro-coil flow probe and cryo probe (coming soon) technology on 500 and 600 MHz machines addresses problems of limited amounts of sample. Another goal is to engage in follow-up studies that employ molecular mechanics data combined with these state-of-the-art NMR techniques.
An additional subject of interest is to explore marine fungi as a source of secondary metabolites. The goal is to isolate novel bioactive substances from fungi cultured from marine sponges in order to discover new structural classes of natural products. We are developing strategies that will maximize the diversity and secondary metabolite production of cultured marine fungi.
Selected Marine Natural Products In Development as Anticancer Drugs:
|
Clin.Trial |
Compound Name | NP Class | Source | Target | Discovering Lab. |
| In Clinical Use | Ectenaiscidin 743 (YondelisTM) | NRP | Tunicate | Tubulin | PharmaMar - Rinehart |
| Phase III | E7389 (halichondrin B inspired) | PK | Synthetic | Tubulin | Eisai |
| Phase II | Dehydrodidemnin B (Aplidine) | PK-NRP | Tunicate | Orn decarboxylase | PharmaMar - Rinehart |
| Phase II | Soblidotin (aka. TZT1027, dola-10 insp.) | NRP | Synthetic | Tubulin | Teikoku - Pettit |
| Phase II | Synthadotin (aka. ILX651, dola-15 insp.) | NRP | Synthetic | Tubulin | ILEX |
| Phase II | Bryostatin 1 | PK-NRP | Bryozoan | PKC | GPC Biotech - Pettit |
| Phase II | Squalamine | Aminosteroid | Shark | Angiogenesis | Zasloff |
| Phase II | Kahalalide F | NRP | Mollusk | Multiple | PharmaMar - Scheuer |
| Phase I | PM02734 (kahalalide insp.) | NRP | Synthetic | Solid tumor | PharmaMar |
| Phase I | Zalypsis (jorumycin insp.) | Alkaloid | Synthetic | DNA | PharmaMar |
| Phase I | E7974 (hemiasterlin insp.) | NRP | Synthetic | Tubulin | Eisai |
| Phase I | Taltobulin (aka.HTI286, hemiasterlin insp.) | NRP | Synthetic | Tubulin | Wyeth - Andersen |
| Phase I | Salinosporamide A (aka. NPI0052) | PK-NRP | Bacteria | Proteasome | Nereus - Fenical |
| Phase I | Spisulosine (aka. ES285) | Lipid | Clam | Rho | PharmaMar |
| Phase I | KRN-7000 (agelasphin insp.) | Lipid | Synthetic | NKT | Koezuka - Kirin |
| Phase I | NPI 2358 (halimide insp.) | Alkaloid | Synthetic | Tubulin | Nereus - Fenical |
| Phase I | LBH 589 (psammaplin insp.) | Alkaloid | Synthetic | HDAC | Novartis |
|
Discontinued |
|||||
| Phase II | Dolastatin 10 | NRP | Sea Hare | Tubulin | Pettit |
| Phase II | Didemnin B | PK-NRP | Tunicate | Antineoplastic | Rinehart |
| Phase II | Cemadotin (dola-15 insp.) | NRP | Synthetic | Tubulin | BASF - Pettit |
| Phase II | Cryptophycin 52 (aka. arenastatin) | NRP | Synthetic | Tubulin | Lilly - Valeriote |
| Phase I | Discodermolide | PK | Sponge | Tubulin | Novartis - HBOI |
| Phase I | LAF 389 (bengamide insp.) | Polyketide | Synthetic | MetAP | Novartis - Crews |
| Phase I | LAQ 824 (psammaplin insp.) | Alkaloid | Synthetic | HDAC | Novartis - Crews |
| Phase I | Girroline (aka. girodazole) | Alkaloid | Sponge | Protein Synthesis | Potier |