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Identification
NameAN2728
Accession NumberDB05219
TypeSmall Molecule
GroupsInvestigational
DescriptionAN2728 is a novel oxaborole in development for the topical treatment of psoriasis. Since psoriasis pathology includes an overproduction of pro-inflammatory and T-cell-produced cytokines, a small molecule that inhibits production of these cytokines without non-specifically inhibiting cellular functions, such as AN2728, is desirable.
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
WeightAverage: 255.077
Monoisotopic: 255.106673785
Chemical FormulaC14H14BNO3
InChI KeyUSQKBFNKMYRGGS-UHFFFAOYSA-N
InChI
InChI=1S/C14H14BNO3/c16-8-10-1-3-12(4-2-10)19-13-5-6-14-11(7-13)9-18-15(14)17/h1-7,17H,8-9,16H2
IUPAC Name
5-[4-(aminomethyl)phenoxy]-1,3-dihydro-2,1-benzoxaborol-1-ol
SMILES
NCC1=CC=C(OC2=CC=C3B(O)OCC3=C2)C=C1
Pharmacology
IndicationIntended for the treatment of psoriasis.
Structured Indications Not Available
PharmacodynamicsAN2728 has broad-spectrum anti-inflammatory activity. It suppresses most pro-inflammatory Th1 and Th2 cytokines. This activity is in the low micromolar range, sufficient for topical application.
Mechanism of actionAN2728 is the product of a focused medicinal chemistry effort to create small molecules that inhibit TNF-alpha, the inflammatory cytokine that is the target of the powerful monoclonal antibodies now marketed for the treatment of psoriasis. Company researchers have shown that AN2728 suppresses the phosphodiesterase 4 (PDE4) enzyme, leading to TNF-alpha inhibition.
TargetKindPharmacological actionActionsOrganismUniProt ID
cAMP-specific 3',5'-cyclic phosphodiesterase 4AProteinunknownNot AvailableHumanP27815 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4BProteinunknownNot AvailableHumanQ07343 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4CProteinunknownNot AvailableHumanQ08493 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4DProteinunknownNot AvailableHumanQ08499 details
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
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9563
Blood Brain Barrier+0.9383
Caco-2 permeable-0.5845
P-glycoprotein substrateNon-substrate0.547
P-glycoprotein inhibitor INon-inhibitor0.8845
P-glycoprotein inhibitor IINon-inhibitor0.8936
Renal organic cation transporterNon-inhibitor0.6515
CYP450 2C9 substrateNon-substrate0.7986
CYP450 2D6 substrateNon-substrate0.7423
CYP450 3A4 substrateNon-substrate0.6599
CYP450 1A2 substrateInhibitor0.5611
CYP450 2C9 inhibitorNon-inhibitor0.6637
CYP450 2D6 inhibitorNon-inhibitor0.706
CYP450 2C19 inhibitorNon-inhibitor0.5344
CYP450 3A4 inhibitorNon-inhibitor0.8253
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.771
Ames testAMES toxic0.5445
CarcinogenicityNon-carcinogens0.8567
BiodegradationNot ready biodegradable0.9645
Rat acute toxicity2.4979 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7405
hERG inhibition (predictor II)Inhibitor0.5739
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 Solubility0.0999 mg/mLALOGPS
logP2ALOGPS
logP1.79ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)8.84ChemAxon
pKa (Strongest Basic)9.59ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area64.71 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity68.35 m3·mol-1ChemAxon
Polarizability27.33 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassEthers
Sub ClassDiarylethers
Direct ParentDiarylethers
Alternative Parents
Substituents
  • Diaryl ether
  • Phenylmethylamine
  • Benzylamine
  • Aralkylamine
  • Benzenoid
  • Monocyclic benzene moiety
  • 1,2-oxaborole derivative
  • Boronic acid ester
  • Boronic acid derivative
  • Oxacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organic metalloid salt
  • Primary amine
  • Organonitrogen compound
  • Organoboron compound
  • Organic metalloid moeity
  • Primary aliphatic amine
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular Weight:
98142.155 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:
PDE4B
Uniprot ID:
Q07343
Molecular Weight:
83342.695 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4C
Uniprot ID:
Q08493
Molecular Weight:
79900.795 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ubiquitin protein ligase binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4D
Uniprot ID:
Q08499
Molecular Weight:
91114.1 Da
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Drug created on October 21, 2007 16:24 / Updated on August 17, 2016 12:24