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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

 

 

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