Identification

Name
Hexachlorophene
Accession Number
DB00756  (APRD00722)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

A chlorinated bisphenol antiseptic with a bacteriostatic action against Gram-positive organisms, but much less effective against Gram-negative organisms. It is mainly used in soaps and creams and is an ingredient of various preparations used for skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797)

Structure
Thumb
Synonyms
  • 2,2'-dihydroxy-3,3',5,5',6,6'-hexachlorodiphenylmethane
  • 2,2'-dihydroxy-3,5,6,3',5',6'-hexachlorodiphenylmethane
  • 2,2'-methanediylbis(3,4,6-trichlorophenol)
  • 2,2'-methylenebis(3,4,6-trichlorophenol)
  • 2,2',3,3',5,5'-hexachloro-6,6'-dihydroxydiphenylmethane
  • bis(2-hydroxy-3,5,6-trichlorophenyl)methane
  • bis(3,5,6-trichloro-2-hydroxyphenyl)methane
  • hexachlorophène
  • Hexachlorophenum
  • Hexaclorofeno
External IDs
NSC-49115 / RCRA Waste Number U132
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PhisohexEmulsion3 %TopicalSanofi Aventis1950-12-312017-03-30Canada
PhisohexEmulsion30 mg/mLTopicalRemedy Repack2013-07-05Not applicableUs
PhisohexEmulsion30 mg/mLTopicalSanofi Aventis1976-06-112017-11-22Us
SapodermLiquid2 %TopicalIngram And Bell Inc.1952-12-311999-08-05Canada
International/Other Brands
Acigena / Aknefug (Dr. August Wolff) / Almederm / Armohex / Dermisan (Armoxindo) / Dial / Distodin / E-Z scrub / Esaclorofene / Exofene / Gamophen / Gamophene / Germa-medica / Hexa-germ / Hexabalm / Hexafen / Hexascrub / Hexide / Nabac / Phiso-scrub / Phisodan / Pre-Op (Davis and Geck) / Pre-Op II / Scrubteam surgical spongebrush / Septi-soft / Septisol / Septofen / Solu-heks / Soy-dome / Staphene O / Ster-zac / Steral / Steraskin / Surgi-cen / Surgi-cin / Surofene / Tersaseptic / Turgex
Categories
UNII
IWW5FV6NK2
CAS number
70-30-4
Weight
Average: 406.904
Monoisotopic: 403.849895678
Chemical Formula
C13H6Cl6O2
InChI Key
ACGUYXCXAPNIKK-UHFFFAOYSA-N
InChI
InChI=1S/C13H6Cl6O2/c14-6-2-8(16)12(20)4(10(6)18)1-5-11(19)7(15)3-9(17)13(5)21/h2-3,20-21H,1H2
IUPAC Name
3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl)methyl]phenol
SMILES
OC1=C(CC2=C(O)C(Cl)=CC(Cl)=C2Cl)C(Cl)=C(Cl)C=C1Cl

Pharmacology

Indication

For use as a surgical scrub and a bacteriostatic skin cleanser. It may also be used to control an outbreak of gram-positive infection where other infection control procedures have been unsuccessful.

Structured Indications
Pharmacodynamics

Hexachlorophene, a detergent cleanser, is an antibacterial sudsing emulsion for topical administration. It is a bacteriostatic cleansing agent. It cleanses the skin thoroughly and has bacteriostatic action against staphylococci and other gram-positive bacteria. Cumulative antibacterial action develops with repeated use. Cleansing with alcohol or soaps containing alcohol removes the antibacterial residue.

Mechanism of action

The primary mechanism of action of hexachlorophene, based on studies with Bacillus megatherium, is to inhibit the membrane-bound part of the electron transport chain, respiratory D-lactate dehydrogenase. It induces leakage, causes protoplast lysis, and inhibits respiration.

TargetActionsOrganism
AD-lactate dehydrogenase
inhibitor
Escherichia coli (strain K12)
ASuccinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
inhibitor
Human
UGlutamate dehydrogenase 1, mitochondrial
inhibitor
Human
UEstrogen receptor alphaNot AvailableHuman
Absorption

Detectable blood levels of hexachlorophene following absorption through intact skin have been found in subjects who regularly scrubbed with hexachlorophene.

Volume of distribution
Not Available
Protein binding

92%

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Oral, rat LD50: 66 mg/kg. Signs of overdose include anorexia, vomiting, abdominal cramps, diarrhea, dehydration, convulsions, hypotension, and shock, and in several reported instances, fatalities.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 2,250,480 U.S. Patent 2,435,593 U.S. Patent 2,812,365

General References
  1. Authors unspecified: Hexachlorophene. IARC Monogr Eval Carcinog Risk Chem Hum. 1979 Oct;20:241-57. [PubMed:397166]
  2. Tyrala EE, Hillman LS, Hillman RE, Dodson WE: Clinical pharmacology of hexachlorophene in newborn infants. J Pediatr. 1977 Sep;91(3):481-6. [PubMed:894425]
  3. Zheng Y, Zhu X, Zhou P, Lan X, Xu H, Li M, Gao Z: Hexachlorophene is a potent KCNQ1/KCNE1 potassium channel activator which rescues LQTs mutants. PLoS One. 2012;7(12):e51820. doi: 10.1371/journal.pone.0051820. Epub 2012 Dec 12. [PubMed:23251633]
External Links
Human Metabolome Database
HMDB14894
KEGG Drug
D00859
KEGG Compound
C08039
PubChem Compound
3598
PubChem Substance
46505858
ChemSpider
3472
BindingDB
31712
ChEBI
5693
ChEMBL
CHEMBL496
Therapeutic Targets Database
DAP001050
PharmGKB
PA449871
HET
H3P
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Hexachlorophene
ATC Codes
D08AE01 — Hexachlorophene
PDB Entries
3ete
MSDS
Download (76.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedPreventionMethicillin Resistant Staphylococcus Aureus Skin Infections1

Pharmacoeconomics

Manufacturers
  • Vestal laboratories div chemed corp
  • Xttrium laboratories inc
  • Huntington laboratories inc
  • Sanofi aventis us llc
  • Bayer pharmaceuticals corp
  • Arbrook inc
  • Dial corp div greyhound co
  • Calgon corp div merck and co inc
  • Becton dickinson and co
  • Professional disposables inc
  • Davis and geck div american cyanamid co
  • 3m co
Packagers
Dosage forms
FormRouteStrength
EmulsionTopical3 %
EmulsionTopical30 mg/mL
LiquidTopical2 %
Prices
Unit descriptionCostUnit
Phisohex 148ml Bottle35.46USD bottle
Hexachlorophene powder11.47USD g
Phisohex 3% cleanser0.18USD ml
Phisohex 473ml Bottle0.13USD ml
Tersaseptic cleanser0.05USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)161-163U.S. Patent 2,435,593.
boiling point (°C)479 °CPhysProp
water solubility140 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP7.54HANSCH,C ET AL. (1995)
pKa4.95HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.000433 mg/mLALOGPS
logP6.77ALOGPS
logP7.08ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)5.15ChemAxon
pKa (Strongest Basic)-7.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity88.59 m3·mol-1ChemAxon
Polarizability34.07 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9935
Blood Brain Barrier+0.9225
Caco-2 permeable+0.8512
P-glycoprotein substrateNon-substrate0.7211
P-glycoprotein inhibitor INon-inhibitor0.9281
P-glycoprotein inhibitor IINon-inhibitor0.9323
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.7848
CYP450 2D6 substrateNon-substrate0.8885
CYP450 3A4 substrateNon-substrate0.653
CYP450 1A2 substrateInhibitor0.8316
CYP450 2C9 inhibitorInhibitor0.9346
CYP450 2D6 inhibitorNon-inhibitor0.7899
CYP450 2C19 inhibitorInhibitor0.9425
CYP450 3A4 inhibitorNon-inhibitor0.7881
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8559
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7953
BiodegradationNot ready biodegradable0.9636
Rat acute toxicity2.4031 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7894
hERG inhibition (predictor II)Non-inhibitor0.841
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.34 KB)
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
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udl-0902800000-eab954bdd46ef95ea0e6
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0903000000-af7e51011b8ac55a0b9c

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
P-chlorophenols / O-chlorophenols / M-chlorophenols / Chlorobenzenes / Aryl chlorides / Organooxygen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Diphenylmethane / 4-halophenol / 3-halophenol / 2-halophenol / 3-chlorophenol / 2-chlorophenol / 4-chlorophenol / Chlorobenzene / Halobenzene / Phenol
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
polyphenol, trichlorobenzene, bridged diphenyl fungicide (CHEBI:5693)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on the ch-oh group of donors, quinone or similar compound as acceptor
Specific Function
First component of the membrane-bound D-lactate oxidase, which is believed to play an important role in the energization of the active transport of a variety of sugars and amino acids.
Gene Name
dld
Uniprot ID
P06149
Uniprot Name
D-lactate dehydrogenase
Molecular Weight
64611.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Wang JL, Buhler DR: Inhibition of dehydrogenase enzymes by hexachlorophene. Biochem Pharmacol. 1978;27(24):2947-53. [PubMed:570044]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquinone binding
Specific Function
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate...
Gene Name
SDHD
Uniprot ID
O14521
Uniprot Name
Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
Molecular Weight
17042.82 Da
References
  1. Lokanatha V, Sailaja P, Rajendra W: In vitro kinetics of the rat brain succinate dehydrogenase inhibition by hexachlorophene. J Biochem Mol Toxicol. 1999;13(6):303-6. [PubMed:10487417]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Nad+ binding
Specific Function
Mitochondrial glutamate dehydrogenase that converts L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in th...
Gene Name
GLUD1
Uniprot ID
P00367
Uniprot Name
Glutamate dehydrogenase 1, mitochondrial
Molecular Weight
61397.315 Da
References
  1. Li M, Smith CJ, Walker MT, Smith TJ: Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics. J Biol Chem. 2009 Aug 21;284(34):22988-3000. doi: 10.1074/jbc.M109.020222. Epub 2009 Jun 15. [PubMed:19531491]
  2. Wang JL, Buhler DR: Inhibition of dehydrogenase enzymes by hexachlorophene. Biochem Pharmacol. 1978;27(24):2947-53. [PubMed:570044]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Jung J, Ishida K, Nishihara T: Anti-estrogenic activity of fifty chemicals evaluated by in vitro assays. Life Sci. 2004 May 7;74(25):3065-74. [PubMed:15081572]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:42