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As of October 2020, shown below are the marine-derived compounds which have either been approved, or are in Phase III, II or I of drug development, and are part of the global marine pharmaceutical clinical pipeline. For a comprehensive review prior to 2011 see A.M.S. Mayer, K.B. Glaser, C. Cuevas, R.S. Jacobs, W. Kem, R.D. Little, J. M McIntosh, D.J. Newman, B.C. Potts and D. E. Shuster, Trends in Pharmacological Sciences, 31:255-265, 2010 TIPS (PDF Doc). This peer-reviewed publication has been cited 678 times (Google Scholar, October 2020). A Global Marine Pharmaceutical Pipeline powerpoint presentation at the 5th IUPHAR World Conference on the Pharmacology of Natural Products, Hyderabad, India (http://www.wcpnaturalproducts.org/), December 2019, is available by clicking the link: https://www.youtube.com/watch?v=vSH_q4ab1hQ&t=10s
Approved Marine Drugs
| Compound Name |
Trademark |
Marine Organism |
Chemical Class |
Molecular Target |
US - Active Clinical Trials |
Europe, Australia- Active Clinical Trials |
Chinese - Active Clinical Trials |
Disease Area |
Company/ Institution |
| Belantamab mafodotin-bl mf |
Blenrep TM (2020)* |
Mollusk/cya nobacterium |
ADC (MMAF) |
BCMA | [9+] | [7+] | None | Cancer: Relapsed/re fractory multiple myeloma |
[GlaxoSmith Kline] |
| Lurbinectedin | Zepzelca TM (2020)* |
Tunicate | Alkaloid | RNA Polymerase II | [6+] | [6+] | None | Cancer: Metastatic Small Cell Lung Cancer |
[Pharmamar] |
| Enfortumab Vedotin-ejfv | PADCEVTM (2019)* | Mollusk/cyanobacterium | ADC (MMAE) | Nectin-4 | [4+] | [3+] | None | Metastatic urothelial cancer | [Astellas Pharma & Seattle Genetics] |
| Polatuzumab vedotin (DCDS-4501A) | Polivy TM (2019)* | Mollusk/ cyanobacterium |
ADC (MMAE) | CD76b & microtubules | [8+] | [4+] | None | Cancer: Non-Hodgkin lymphoma, Chronic lymphocytic leukemia, Lymphoma, B-Cell lymphoma, Folicular | [Genetech/ Roche] |
| Plitidepsin** | Aplidin® | Tunicate | Depsipeptide | eEF1A2 | [1+] | [6+] | None | Cancer: Multiple Myeloma, Leukemia, Lymphoma | [Pharmamar] |
| Trabectedin (ET-743) |
Yondelis® (2015) * |
Tunicate | Alkaloid | Minor groove of DNA | [32+] | [28+] | None | Cancer: Soft Tissue Sarcoma and Ovarian Cancer | [Pharmamar] |
| Brentuximab vedotin (SGN-35) |
Adcetris® (2011) * |
Mollusk/ cyanobacterium |
ADC(MMAE) | CD30 & microtubules | [79+] | [37+] | None | Cancer: Anaplastic large T-cell systemic maglinant lymphoma, Hodgkin's disease | [Seattle Genetics] |
| Eribulin Mesylate (E7389) | Halaven® (2010) * |
Sponge | Macrolide | Microtubules | [46+] | [11+] | None | Cancer: Metastatic Breast Cancer | [Eisai Inc.] |
| Omega-3-acid ethyl esters | Lovaza® (2004) * |
Fish | Omega-3 fatty acids | Trygliceride-synthesizing enzymes | [1+] | None | None | Hypertriglyceridemia | [Glaxo Smith Kline] |
| Eicosapenta enoic acid ethyl ester |
Vascepa® (2012)* | Fish | Omega-3 fatty acids |
Triglyceridesynthesizing enzymes |
[6+] | [3+] | None | Hypertriglyc eridemia |
[Amarin] |
| Omega-3-ca rboxylic acid |
Epanova® (2014)* | Fish | Omega-3 fatty acids |
Triglyceridesynthesizing enzymes |
[1+] | [6+] | None | Hypertriglyc eridemia |
[AstraZeneca] |
| Ziconotide | Prialt® (2004) * |
Cone snail | Peptide | N-TypeCa channel | [2+] | [3+] | None | Pain: Severe Chronic Pain | [Jazz Pharmaceuticals] |
| Vidarabine (Ara-A) |
Vira-A® (1976)* |
Sponge | Nucleoside | Viral DNA polymerase | [162+] | None | None | Antiviral: Herpes Simplex Virus | [Mochida Pharmaceutical Co.] |
| Cytarabine (Ara-C) |
Cytosar-U® (1969) * |
Sponge | Nucleoside | DNA polymerase | [462+] | [140+] | [23+] | Cancer:Leukemia | [Pfizer] |
* FDA Years Approved ** Australia Dec 2018 Approved.
PHASE III CLINICAL STATUS
| Compound Name |
Trademark | Marine Organism |
Chemical Class |
Molecular Target |
US - Active Clinical Trials |
Europe - Active Clinical Trials |
Chinese - Active Clinical Trials |
Disease Area |
Company/ Institution |
| Plinabulin (NPI-2358) |
NA | Fungus | Diketopiperazine | Microtubules | [5+] | None | None | Cancer: Non-Small Cell Lung Cancer, Brain Tumor | [BeyondSpring Pharmaceuticals] |
| Tetrodotoxin | Halneuron TM | Pufferfish | Guanidinium alkaloid | Sodium Channel | [1+] | None | None | Pain: Chronic Pain | [Wex Pharmaceutical Inc.] |
| Lurbinectedin (PM01183) | ZepzelkaTM | Tunicate | Alkaloid | RNA Polymerase II | [5+] | [4+] | None | Cancer: Ovarian Cancer, Breast Cancer, SCLC | [Pharmamar] |
| Marizomib (Salinosporamide A; NPI-0052) | NA | Bacterium | Beta-lactone-gamma lactam | 20S proteasome | [4+] | [1+] | None | Cancer: Non-Small Cell Lung Cancer, Pancreatic Cancer, Melanoma, Lymphoma, Multiple Myeloma | [Triphase] |
PHASE II CLINICAL STATUS
| Compound Name |
Trademark | Marine Organism |
Chemical Class |
Molecular Target |
US - Active Clinical Trials |
Europe - Active Clinical Trials |
Chinese - Active Clinical Trials |
Disease Area |
Company/ Institution |
| GTS-21 (DMXBA) |
NA | Worm | Alkaloid | α7 nicotinic acetylcholine receptor | [1+] | None | None | Schizophrenia, Alzheimer Disease, Attention Deficit Hyperactivity Disorder, Endotoxemia, Sepsis, Vagal Activity | No Link |
| AGS-16C3F | NA | Mollusk/ cyanobacterium |
ADC (MMAF) | ENPP3 & microtubules | [1+] | None | None | Cancer: Renal Cell Carcinoma | [Agensys & Astellas Pharma] |
| Plocabulin (PM184) |
NA | Sponge | Polyketide | Minor groove of DNA | [1+] | None | None | Cancer: Solid Tumors | [Pharmamar] |
| Tisotumab Vedotin | HuMax®-TF-ADC | Mollusk/ cyanobacterium | ADC (MMAE) | Tissue Factor & microtubules | [5+] | [4+] | None | Cancer: Ovary Cancer, Cervix Cancer, Endometrium Cancer, Bladder Cancer, Prostate Cancer (CRPC), Cancer of Head and Neck (SCCHN), Esophagus Cancer, Lung Cancer (NSCLC) | [GenMab] |
| Ladiratuzumab vedotin (SGN-LIV1A) |
NA | Mollusk/ cyanobacterium |
ADC (MMAE) | LIV-1 & microtubules | [5+] | [2+] | None | Cancer: Breast Cancer | [Seattle Genetics] |
| Bryostatin | NA | Bryozoan | Macrolide Iactone |
Protein kinase C | [1+] | None | None | Alzheimer's Disease | [ Neurotrope BioScience] |
| Telisotuzumab vedotin (ABBV-399) |
NA | Mollusk/ cyanobacterium | ADC (MMAE) | c-Met | [3+] | [1+] | None | Cancer: Solid tumors | [Abbvie] |
| Enapotamab vedotin (HuMax-AXL) | NA | Mollusk/ cyanobacterium | ADC (MMAE) | Axl RTK | [1+] | None | None | Cancer: Ovarian Cancer, Cervical Cancer, Endometrial Cancer | [Genmab] |
| RC-48 | NA | Mollusk/ cyanobacterium | ADC (MMAE) | HER2 | [4+] | None | None | Cancer: Urothelial Carcinoma, Advanced Cancer, Gastric Cancer, HER2 Overexpressing Gastric Carcinoma, Advanced Breast Cancer, Solid Tumors | [RemeGen] |
| CAB-ROR2 (BA-3021) | NA | Mollusk/ cyanobacterium | ADC (MMAE) | ROR2 | [1+] | None | None | Cancer: Solid Tumor, Non Small Cell Lung Cancer, Triple Negative Breast Cancer, Soft Tissue Sarcoma | [BioAtla] |
| CX-2029 (ABBV-2029) | NA | Mollusk/ cyanobacterium | ADC (MMAE) | CD71 | [1+] | [1+] | None | Cancer: Solid Tumor, Head and Neck Cancer, Non Small Cell Lung Cancer, Pancreatic Cancer, Diffuse Large B Cell Lymphoma | [AbbVie & CytomX Therapeutics] |
| W0101 | NA | Mollusk/ cyanobacterium | ADC (MMAE) | IGF-R1 | [1+] | [1+] | None | Cancer: Advanced or Metastatic Solid Tumors | [Pierre-Fabre] |
PHASE I CLINICAL STATUS
| Compound Name |
Trademark | Marine Organism |
Chemical Class |
Molecular Target |
US - Active Clinical Trials |
Europe - Active Clinical Trials |
Chinese - Active Clinical Trials |
Disease Area |
Company/ Institution |
| ARX-788 | NA | Mollusk/ cyanobacterium | ADC (MMAE) | HER2 & microtubules | [1+] |
None | None | Cancer: Breast Cancer, Gastric Cancer | [Ambrex & Zhejiang Medicine] |
| XMT-1536 | NA | Mollusk/ cyanobacterium | ADC (Dolaflexin) | NaPi2b & microtubules | [1+] | None | None | Cancer: Solid tumors | [Mersana Therapeutics] |
| ALT-P7 | NA | Mollusk/ cyanobacterium | ADC (MMAE) | HER2 & microtubules | [1+] | None | None | Cancer: Breast cancer, Gastric cancer | [3SBio & Alteogen] |
| MORAb-202 | NA | Sponge | ADC (Macrolide) | Microtubules | [1+] | None | None | Cancer: Solid Tumors | [Eisai] |
| PF-06804103 | NA | Mollusk/cyanobacterium | ADC (Auristatin variant) | HER2 | [1+] | None | None | Cancer: Breast Neoplasms, Stomach Neoplasms, Esophagogastric Junction Neoplasm, Carcinoma, Non-small-cell Lung | [Pfizer & AbbVie] |
| Griffithsin | NA | Red alga | Lectin | Carbohydrate-binding | [1+] | NA | NA | HIV prevention | [Center for Predictive Medicine] |
| ZW-49 | NA | Mollusk/cyanobacterium | ADC (Auristatin variant) | HER2 | [1+] | None | None | Cancer: HER2-expressing Cancers | [Zymeworks & BeiGene] |
ABBREVIATIONS:
- ADC: Antibody Drug Conjugate;
- Ara-A: 9-β-D-arabinofuranosyladenine
- Ara-C: Cytosine Arabinoside
- BCMA: B-cell Maturation Antigen
- CD: Cluster of Differentiation;
- c-Met: Tyrosine-Protein Kinase Met
- DMXBA: 3-(2,4-Dimethoxybenzylidene)-Anabaseine
- EGFR: Epidermal Growth Factor Receptor;
- ENPP3: Ectonucleotide Pyrophosphatase/Phosphodiesterase Family Member 3
- FDA: Food and Drug Administration;
- GPNMB: Glycoprotein nonmetastatic B;
- LIV-1: Zinc transporter SLC39A6;
- LRRC15: Leucine rich repeat containing 15
- MMAE: Monomethylauristatin E;
- MMAF: Monomethylauristatin F;
- NaPi2b: Sodium-Dependent Phosphate Transport Protein 2b;
- PSMA: Prostate-Specific Membrane Antigen;
- TIM-1: T-cell Immunoglobulin domain 1