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Identification
NameE7389
Accession NumberDB04940
TypeSmall Molecule
GroupsInvestigational
Description

E7389 is being studied in the treatment of cancer. It belongs to the family of drugs called antitubulin agents. It is the synthetic form of Halichondrin B (NSC 609395), a macrocyclic polyether initially isolated from the sponge Halichondria okadai.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIINot Available
CAS numberNot Available
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Taxonomy
ClassificationNot classified
Pharmacology
IndicationInvestigated for use/treatment in breast cancer, cancer/tumors (unspecified), head and neck cancer, lung cancer, prostate cancer, and sarcoma.
PharmacodynamicsE7389, like its parent natural compound Halichondrin B, is classified as a tubulin depolymerizer, and it shows activity at least equal to the naturally occurring chemical. It acts to disrupt the polymerization of the microtubules necessary in mitosis.2 This general characteristic places E7389 in the group of drugs that includes Vinca alkaloids, dolastatins, cryptophycin, and so forth, but its tubulin interactions appear to be unique, and it was found to have greater activity against lung and breast tumors in animal studies than either the parent halichondrin B or paclitaxel.
Mechanism of actionE7389 can activate cellular apoptosis pathways under anchorage-independent and -dependent cell culture conditions. Prolonged mitotic blockage by E7389 can lead to apoptotic cell death of human cancer cells in vitro and can provide a mechanistic basis for the significant in vivo anticancer efficacy of E7389.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
References
Synthesis ReferenceNot Available
General References
  1. Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA: Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res. 2004 Aug 15;64(16):5760-6. [PubMed:15313917 ]
  2. Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L: The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 2005 Jul;4(7):1086-95. [PubMed:16020666 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ubiquitin protein ligase binding
Specific Function:
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating f...
Gene Name:
BCL2
Uniprot ID:
P10415
Molecular Weight:
26265.66 Da
References
  1. Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA: Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res. 2004 Aug 15;64(16):5760-6. [PubMed:15313917 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Structural constituent of cytoskeleton
Specific Function:
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
Gene Name:
TUBB1
Uniprot ID:
Q9H4B7
Molecular Weight:
50326.56 Da
References
  1. Dabydeen DA, Burnett JC, Bai R, Verdier-Pinard P, Hickford SJ, Pettit GR, Blunt JW, Munro MH, Gussio R, Hamel E: Comparison of the activities of the truncated halichondrin B analog NSC 707389 (E7389) with those of the parent compound and a proposed binding site on tubulin. Mol Pharmacol. 2006 Dec;70(6):1866-75. Epub 2006 Aug 29. [PubMed:16940412 ]
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Drug created on October 21, 2007 16:23 / Updated on September 13, 2013 11:56