Clinical Pipeline

Marine Pharmacology

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 

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