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Identification
NameLatrunculin A
Accession NumberDB02621  (EXPT02004)
TypeSmall Molecule
GroupsExperimental
Description

Latrunculin A is an actin binding macrolide purified from the red sea sponge Latrunculia magnifica. It is under investigation for the treatment of cancer. It disrupts actin polymerization, prevents mitotic spindle formation and thus cell replication.

Structure
Thumb
Synonyms
(+)-latrunculin A
(4R)-4-[(1R,4Z,8E,10Z,12S,15R,17R)-17-hydroxy-5,12-dimethyl-3-oxo-2,16-dioxabicyclo[13.3.1]nonadeca-4,8,10-trien-17-yl]-1,3-thiazolidin-2-one
LAT-A
LatA
External Identifiers
  • NSC-613011
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
CategoriesNot Available
UNIISRQ9WWM084
CAS number76343-93-6
WeightAverage: 421.55
Monoisotopic: 421.192293797
Chemical FormulaC22H31NO5S
InChI KeyDDVBPZROPPMBLW-IZGXTMSKSA-N
InChI
InChI=1S/C22H31NO5S/c1-15-7-5-3-4-6-8-16(2)11-20(24)27-18-12-17(10-9-15)28-22(26,13-18)19-14-29-21(25)23-19/h3-5,7,11,15,17-19,26H,6,8-10,12-14H2,1-2H3,(H,23,25)/b4-3+,7-5-,16-11-/t15-,17-,18-,19+,22-/m1/s1
IUPAC Name
(1R,4Z,8E,10Z,12S,15R,17R)-17-hydroxy-17-[(4R)-2-hydroxy-4,5-dihydro-1,3-thiazol-4-yl]-5,12-dimethyl-2,16-dioxabicyclo[13.3.1]nonadeca-4,8,10-trien-3-one
SMILES
[H]\C1=C(\[H])/C(/[H])=C([H])\[C@@]([H])(C)CC[C@]2([H])C[C@]([H])(C[C@@](O)(O2)[C@]2([H])CSC(O)=N2)OC(=O)\C([H])=C(C)/CC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as macrolides and analogues. These are organic compounds containing a lactone ring of at least twelve members.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolides and analogues
Sub ClassNot Available
Direct ParentMacrolides and analogues
Alternative Parents
Substituents
  • Macrolide
  • Oxane
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Thiazolidine
  • Lactone
  • Hemiacetal
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Thioether
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationNot Available
PharmacodynamicsNot Available
Mechanism of actionNot Available
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 organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8669
Blood Brain Barrier-0.7361
Caco-2 permeable-0.648
P-glycoprotein substrateSubstrate0.7253
P-glycoprotein inhibitor INon-inhibitor0.9156
P-glycoprotein inhibitor IINon-inhibitor0.9955
Renal organic cation transporterNon-inhibitor0.9178
CYP450 2C9 substrateNon-substrate0.8784
CYP450 2D6 substrateNon-substrate0.7988
CYP450 3A4 substrateSubstrate0.5818
CYP450 1A2 substrateNon-inhibitor0.7734
CYP450 2C9 inhibitorNon-inhibitor0.8112
CYP450 2D6 inhibitorNon-inhibitor0.9139
CYP450 2C19 inhibitorNon-inhibitor0.7337
CYP450 3A4 inhibitorNon-inhibitor0.9704
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9312
Ames testNon AMES toxic0.7094
CarcinogenicityNon-carcinogens0.9597
BiodegradationNot ready biodegradable0.5156
Rat acute toxicity2.6858 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9838
hERG inhibition (predictor II)Non-inhibitor0.9342
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 Properties
PropertyValueSource
Water Solubility0.0195 mg/mLALOGPS
logP3.52ALOGPS
logP5.13ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)7.37ChemAxon
pKa (Strongest Basic)1.17ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area88.35 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity116.48 m3·mol-1ChemAxon
Polarizability44.96 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Coue M, Brenner SL, Spector I, Korn ED: Inhibition of actin polymerization by latrunculin A. FEBS Lett. 1987 Mar 23;213(2):316-8. [PubMed:3556584 ]
  2. Konishi H, Kikuchi S, Ochiai T, Ikoma H, Kubota T, Ichikawa D, Fujiwara H, Okamoto K, Sakakura C, Sonoyama T, Kokuba Y, Sasaki H, Matsui T, Otsuji E: Latrunculin a has a strong anticancer effect in a peritoneal dissemination model of human gastric cancer in mice. Anticancer Res. 2009 Jun;29(6):2091-7. [PubMed:19528469 ]
  3. Foissner I, Wasteneys GO: Wide-ranging effects of eight cytochalasins and latrunculin A and B on intracellular motility and actin filament reorganization in characean internodal cells. Plant Cell Physiol. 2007 Apr;48(4):585-97. Epub 2007 Feb 27. [PubMed:17327257 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Structural constituent of cytoskeleton
Specific Function:
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:
ACTA1
Uniprot ID:
P68133
Molecular Weight:
42050.67 Da
References
  1. Coue M, Brenner SL, Spector I, Korn ED: Inhibition of actin polymerization by latrunculin A. FEBS Lett. 1987 Mar 23;213(2):316-8. [PubMed:3556584 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein domain specific binding
Specific Function:
Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed. Plays a role in ciliogenesis.
Gene Name:
GSN
Uniprot ID:
P06396
Molecular Weight:
85696.935 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Clostridium perfringens
Pharmacological action
unknown
General Function:
Nucleotide binding
Specific Function:
Not Available
Gene Name:
Not Available
Uniprot ID:
Q46220
Molecular Weight:
52316.715 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
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Drug created on June 13, 2005 07:24 / Updated on May 12, 2016 14:06