Identification

Name
Solabegron
Accession Number
DB06190
Type
Small Molecule
Groups
Investigational
Description

Solabegron (GW-427,353) is a drug which acts as a selective agonist for the β3 adrenergic receptor. It is being developed for the treatment of overactive bladder and irritable bowel syndrome.

Structure
Thumb
Synonyms
Not Available
External IDs
GW 427353
Product Ingredients
IngredientUNIICASInChI Key
Solabegron hydrochlorideGU14FR8D4A451470-34-1PMXCGBVBIRYFPR-FTBISJDPSA-N
Categories
UNII
55P6YH9O6N
CAS number
252920-94-8
Weight
Average: 410.9
Monoisotopic: 410.1397203
Chemical Formula
C23H23ClN2O3
InChI Key
LLDXOPKUNJTIRF-QFIPXVFZSA-N
InChI
InChI=1S/C23H23ClN2O3/c24-20-8-2-6-18(13-20)22(27)15-25-10-11-26-21-9-3-5-17(14-21)16-4-1-7-19(12-16)23(28)29/h1-9,12-14,22,25-27H,10-11,15H2,(H,28,29)/t22-/m0/s1
IUPAC Name
3'-[(2-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}ethyl)amino]-[1,1'-biphenyl]-3-carboxylic acid
SMILES
[H][C@](O)(CNCCNC1=CC(=CC=C1)C1=CC(=CC=C1)C(O)=O)C1=CC=CC(Cl)=C1

Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 2, irritable bowel syndrome (IBS), and urinary incontinence.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UBeta-3 adrenergic receptor
agonist
Human
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
DrugInteraction
AcebutololThe therapeutic efficacy of Solabegron can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Solabegron.
AlfuzosinThe therapeutic efficacy of Solabegron can be decreased when used in combination with Alfuzosin.
AmitriptylineThe therapeutic efficacy of Solabegron can be decreased when used in combination with Amitriptyline.
AmoxapineAmoxapine may decrease the vasoconstricting activities of Solabegron.
AripiprazoleAripiprazole may decrease the vasoconstricting activities of Solabegron.
AsenapineAsenapine may decrease the vasoconstricting activities of Solabegron.
AtenololThe therapeutic efficacy of Solabegron can be decreased when used in combination with Atenolol.
Benzylpenicilloyl PolylysineSolabegron may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetaxololThe therapeutic efficacy of Solabegron can be decreased when used in combination with Betaxolol.
Food Interactions
Not Available

References

General References
  1. Grudell AB, Camilleri M, Jensen KL, Foxx-Orenstein AE, Burton DD, Ryks MD, Baxter KL, Cox DS, Dukes GE, Kelleher DL, Zinsmeister AR: Dose-response effect of a beta3-adrenergic receptor agonist, solabegron, on gastrointestinal transit, bowel function, and somatostatin levels in health. Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1114-9. doi: 10.1152/ajpgi.00051.2008. Epub 2008 Mar 27. [PubMed:18372395]
  2. Hicks A, McCafferty GP, Riedel E, Aiyar N, Pullen M, Evans C, Luce TD, Coatney RW, Rivera GC, Westfall TD, Hieble JP: GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog. J Pharmacol Exp Ther. 2007 Oct;323(1):202-9. Epub 2007 Jul 12. [PubMed:17626794]
External Links
PubChem Compound
9887812
PubChem Substance
347827760
ChemSpider
8063484
BindingDB
50002595
ChEMBL
CHEMBL208427
Wikipedia
Solabegron

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticIrritable Bowel Syndrome (IBS)1
1CompletedTreatmentUrinary Bladder, Overactive2
2CompletedTreatmentUrinary Bladder, Overactive1
2RecruitingTreatmentUrinary Bladder, Overactive1

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 Solubility0.00167 mg/mLALOGPS
logP3.67ALOGPS
logP1.61ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)4.01ChemAxon
pKa (Strongest Basic)9.02ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area81.59 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity116.75 m3·mol-1ChemAxon
Polarizability45.24 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9399
Blood Brain Barrier+0.7481
Caco-2 permeable-0.5411
P-glycoprotein substrateSubstrate0.7467
P-glycoprotein inhibitor INon-inhibitor0.8542
P-glycoprotein inhibitor IINon-inhibitor0.8907
Renal organic cation transporterNon-inhibitor0.7937
CYP450 2C9 substrateNon-substrate0.7838
CYP450 2D6 substrateNon-substrate0.8299
CYP450 3A4 substrateNon-substrate0.6663
CYP450 1A2 substrateInhibitor0.5132
CYP450 2C9 inhibitorNon-inhibitor0.6705
CYP450 2D6 inhibitorNon-inhibitor0.6447
CYP450 2C19 inhibitorNon-inhibitor0.6671
CYP450 3A4 inhibitorNon-inhibitor0.8394
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7415
Ames testNon AMES toxic0.5071
CarcinogenicityNon-carcinogens0.7194
BiodegradationNot ready biodegradable0.9856
Rat acute toxicity2.5218 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7658
hERG inhibition (predictor II)Inhibitor0.5771
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 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 biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
Benzoic acids / Phenylalkylamines / Aniline and substituted anilines / Benzoyl derivatives / Secondary alkylarylamines / Chlorobenzenes / Aryl chlorides / Secondary alcohols / 1,2-aminoalcohols / Amino acids
show 8 more
Substituents
Biphenyl / Benzoic acid or derivatives / Benzoic acid / Benzoyl / Aniline or substituted anilines / Phenylalkylamine / Chlorobenzene / Halobenzene / Secondary aliphatic/aromatic amine / Aralkylamine
show 24 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 Da
References
  1. Grudell AB, Camilleri M, Jensen KL, Foxx-Orenstein AE, Burton DD, Ryks MD, Baxter KL, Cox DS, Dukes GE, Kelleher DL, Zinsmeister AR: Dose-response effect of a beta3-adrenergic receptor agonist, solabegron, on gastrointestinal transit, bowel function, and somatostatin levels in health. Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1114-9. doi: 10.1152/ajpgi.00051.2008. Epub 2008 Mar 27. [PubMed:18372395]

Drug created on March 19, 2008 10:16 / Updated on August 02, 2018 07:58