Identification

Name
Latrunculin A
Accession Number
DB02621  (EXPT02004)
Type
Small Molecule
Groups
Experimental
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 IDs
NSC-613011
Categories
UNII
SRQ9WWM084
CAS number
76343-93-6
Weight
Average: 421.55
Monoisotopic: 421.192293797
Chemical Formula
C22H31NO5S
InChI Key
DDVBPZROPPMBLW-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])\[[email protected]@]([H])(C)CC[[email protected]]2([H])C[[email protected]]([H])(C[[email protected]@](O)(O2)[[email protected]]2([H])CSC(O)=N2)OC(=O)\C([H])=C(C)/CC1

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UActin, alpha skeletal muscle
inhibitor
Human
UGelsolinNot AvailableHuman
UIota toxin component IaNot AvailableClostridium perfringens
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
PubChem Compound
6437378
PubChem Substance
46508901
ChemSpider
393069
BindingDB
50235955
ChEBI
69136
ChEMBL
CHEMBL404116
HET
LAR
PDB Entries
1esv / 1ijj / 1lcu / 1rdw / 1rfq / 1sqk / 2a5x / 2q1n / 2q31 / 3buz
show 7 more

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolides and analogues
Sub Class
Not Available
Direct Parent
Macrolides and analogues
Alternative Parents
Oxanes / Thiazolidines / Enoate esters / Thiocarbamic acid derivatives / Organic carbonic acids and derivatives / Lactones / Hemiacetals / Oxacyclic compounds / Monocarboxylic acids and derivatives / Azacyclic compounds
show 5 more
Substituents
Macrolide / Oxane / Thiazolidine / Enoate ester / Alpha,beta-unsaturated carboxylic ester / Carboxylic acid ester / Hemiacetal / Lactone / Carbonic acid derivative / Thiocarbamic acid derivative
show 14 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
cyclic hemiketal, macrolide, oxabicycloalkane, thiazolidinone (CHEBI:69136)

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
Uniprot Name
Actin, alpha skeletal muscle
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 assembl...
Gene Name
GSN
Uniprot ID
P06396
Uniprot Name
Gelsolin
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
Uniprot Name
Iota toxin component Ia
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]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 15:00