Botulinum toxin (T3D3583)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2009-08-12 19:45:06 UTC
Update Date2014-12-24 20:26:11 UTC
Accession NumberT3D3583
Identification
Common NameBotulinum toxin
ClassProtein
DescriptionBotulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum. Though it is the most toxic protein known, it may be used in minute doses to treat muscle spasms and in cosmetic treatment, under the brand name Botox. (6)
Compound Type
  • Amide
  • Amine
  • Anti-Wrinkle Agent
  • Antidystonic Agent
  • Bacterial Toxin
  • Natural Compound
  • Neuromuscular Blocking Agent
  • Organic Compound
  • Protein
  • Shigella Toxin
Protein StructureT3d3583
Synonyms
Synonym
BoNT/A
Bontoxilysin A
Botox
BOTOX Cosmetic
Botulinum neurotoxin type A precursor
BTX-A
Dysport
Xeomin
Chemical FormulaNot Available
Average Molecular Mass149452.615 g/mol
CAS Registry Number93384-43-1
SequenceNot Available
Chemical Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceClear solution.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted PropertiesNot Available
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Toxicity Profile
Route of ExposureThe chemical complexity of Botulinum Toxin Type A combined with its extreme potency limits the opportunity to study its pharmacokinetic profile in humans. Therefore, no human pharmacokinetic studies have been performed. Botulinum Toxin Type A is injected directly into the target organ, a skeletal muscle. Thus, bioavailability of the intravenous or oral route is not of clinical relevance. Oral (7) ; inhalation (7) ; dermal contact (if access to bloodstream) (7).
Mechanism of ToxicityBotulinum toxin is a two-chain polypeptide with a 100-kDa heavy chain joined by a disulfide bond to a 50-kDa light chain. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to cleave endocytotic vesicles and reach the cytoplasm. The light chain has protease activity and proteolytically degrades the SNAP-25 protein at neuromuscular junctions, preventing vesicles from anchoring to the membrane to release acetylcholine. By inhibiting acetylcholine release, the toxin interferes with nerve impulses and causes flaccid (sagging) paralysis of muscles. (6)
MetabolismFree toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases.
Toxicity ValuesBased on toxicological studies, it has been estimated that the human LD50 by injection is approximately 2800 Units, equivalent to 28 individual vials of BOTOX (Botulinum Toxin Type A) Purified Neurotoxin Complex (100 Units) for a 70 kg adult.
Lethal Dose1 nanogram/kg for an adult human. (6)
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesBotulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum. Though it is the most toxic protein known, it may be used in minute doses to treat muscle spasms and in cosmetic treatment, under the brand name Botox (6). For the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia. Also for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents and for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above. Also used cosmetically to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) as well as for the treatment of excessive underarm sweating.
Minimum Risk LevelNot Available
Health EffectsBotulinum toxin is an extremely potent neurotoxin that causes paralysis. Death may result from respiratory failure following paralysis of the respiratory muscles. (6)
SymptomsAdverse effects from the cosmetic use of botulinum toxin include headaches, focal facial paralysis, muscle weakness, dysphagia, flu-like syndromes, and allergic reactions. (6)
TreatmentTreatment consists of antitoxin administration and artificial ventilation until the neurotoxins are excreted or metabolised. The two primary botulinum antitoxins are Trivalent (A,B,E) Botulinum Antitoxin and Heptavalent (A,B,C,D,E,F,G) Botulinum Antitoxin. (6)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00083
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDC07946
UniProt IDP10845
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBotulinum toxin
PDB ID1UEE
ACToR IDNot Available
Wikipedia LinkBotox
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Montecucco C, Molgo J: Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol. 2005 Jun;5(3):274-9. [15907915 ]
  2. Brin MF, Lew MF, Adler CH, Comella CL, Factor SA, Jankovic J, O'Brien C, Murray JJ, Wallace JD, Willmer-Hulme A, Koller M: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology. 1999 Oct 22;53(7):1431-8. [10534247 ]
  3. Shukla HD, Sharma SK: Clostridium botulinum: a bug with beauty and weapon. Crit Rev Microbiol. 2005;31(1):11-8. [15839401 ]
  4. Eisenach JH, Atkinson JL, Fealey RD: Hyperhidrosis: evolving therapies for a well-established phenomenon. Mayo Clin Proc. 2005 May;80(5):657-66. [15887434 ]
  5. Schurch B, Corcos J: Botulinum toxin injections for paediatric incontinence. Curr Opin Urol. 2005 Jul;15(4):264-7. [15928517 ]
  6. Wikipedia. Botulinum toxin. Last Updated 12 August 2009. [Link]
  7. Wikipedia. Bacterial toxin. Last Updated 27 February 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Synaptosomal-associated protein 25
General Function:
Syntaxin-1 binding
Specific Function:
t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells.
Gene Name:
SNAP25
Uniprot ID:
P60880
Molecular Weight:
23314.905 Da
References
  1. Zhou JY, Wang ZF, Ren XM, Tang MZ, Shi YL: Antagonism of botulinum toxin type A-induced cleavage of SNAP-25 in rat cerebral synaptosome by toosendanin. FEBS Lett. 2003 Dec 4;555(2):375-9. [14644446 ]
  2. Flynn TC: Myobloc. Dermatol Clin. 2004 Apr;22(2):207-11, vii. [15222581 ]
  3. Okada M, Yoshida S, Zhu G, Kaneko S: [Methodological consideration in studying the exocytosis mechanisms using microdialysis]. Nihon Shinkei Seishin Yakurigaku Zasshi. 2004 Aug;24(4):165-70. [15484814 ]
  4. Frassoni C, Inverardi F, Coco S, Ortino B, Grumelli C, Pozzi D, Verderio C, Matteoli M: Analysis of SNAP-25 immunoreactivity in hippocampal inhibitory neurons during development in culture and in situ. Neuroscience. 2005;131(4):813-23. [15749336 ]
  5. Straughan D: Progress in applying the Three Rs to the potency testing of Botulinum toxin type A. Altern Lab Anim. 2006 Jun;34(3):305-13. [16831062 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
2. Rho-related GTP-binding protein RhoB
General Function:
Gtpase activity
Specific Function:
Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.
Gene Name:
RHOB
Uniprot ID:
P62745
Molecular Weight:
22123.185 Da
References
  1. Ishida H, Zhang X, Erickson K, Ray P: Botulinum toxin type A targets RhoB to inhibit lysophosphatidic acid-stimulated actin reorganization and acetylcholine release in nerve growth factor-treated PC12 cells. J Pharmacol Exp Ther. 2004 Sep;310(3):881-9. Epub 2004 May 12. [15140914 ]