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Accession NumberDB05016
TypeSmall Molecule

PTC124 is a novel, orally administered drug that targets nonsense mutations and is being investigated initially as a treatment for Duchenne muscular dystrophy (DMD) and cystic fibrosis (CF), with the potential to treat a number of other genetic disorders caused by nonsense mutations.

EC-000.2051Not AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS numberNot Available
WeightAverage: 284.242
Monoisotopic: 284.059720369
Chemical FormulaC15H9FN2O3
3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid
Mass SpecNot Available
KingdomOrganic Compounds
ClassBenzene and Substituted Derivatives
SubclassBenzoic Acid and Derivatives
Direct parentBenzoic Acids
Alternative parentsBenzoyl Derivatives; Fluorobenzenes; Aryl Fluorides; Oxadiazoles; Enolates; Polyamines; Carboxylic Acids; Organofluorides
Substituentsbenzoyl; fluorobenzene; aryl fluoride; aryl halide; oxadiazole; azole; enolate; polyamine; carboxylic acid; carboxylic acid derivative; organohalogen; organofluoride; organonitrogen compound
Classification descriptionThis compound belongs to the benzoic acids. These are organic Compounds containing a benzene ring which bears at least one carboxyl group.
IndicationInvestigated for use/treatment in cystic fibrosis and muscular dystrophy.
PharmacodynamicsNot Available
Mechanism of actionPTC124 allowed the cellular machinery to bypass the nonsense mutation, continue the translation process, and thereby restore the production of a full-length, functional protein. The research on the effects of PTC124 on the translation and stability of nonsense-containing mRNA in vitor show that PTC124 promoted readthrough at each of the nonsense codons, showing maximal activity with UGA, while having no effect on mRNA levels. Unlike the stable cell line assays, PTC124 did not discriminate significantly between the UAG and UAA mRNAs. PTC124 was a more potent nonsense-suppressing agent than gentamicin, and exhibited 4- to 15-fold stimulation of in vitro readthrough relative to the controls at levels similar to those in the stable cell reporter assays. These results indicate that PTC124 modulates termination efficiency at premature nonsense codons.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Route of eliminationNot Available
Half life3-6 hours
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9681
Caco-2 permeable - 0.5391
P-glycoprotein substrate Non-substrate 0.8144
P-glycoprotein inhibitor I Non-inhibitor 0.8905
P-glycoprotein inhibitor II Non-inhibitor 0.9784
Renal organic cation transporter Non-inhibitor 0.9401
CYP450 2C9 substrate Non-substrate 0.8214
CYP450 2D6 substrate Non-substrate 0.8367
CYP450 3A4 substrate Non-substrate 0.661
CYP450 1A2 substrate Inhibitor 0.7977
CYP450 2C9 substrate Non-inhibitor 0.7856
CYP450 2D6 substrate Non-inhibitor 0.885
CYP450 2C19 substrate Inhibitor 0.5857
CYP450 3A4 substrate Non-inhibitor 0.8332
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5533
Ames test Non AMES toxic 0.7057
Carcinogenicity Non-carcinogens 0.7693
Biodegradation Not ready biodegradable 0.9828
Rat acute toxicity 2.3907 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.997
hERG inhibition (predictor II) Non-inhibitor 0.8984
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Experimental PropertiesNot Available
Predicted Properties
Water Solubility0.117ALOGPS
pKa (Strongest Acidic)3.9ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area76.22 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity94.66 m3·mol-1ChemAxon
Polarizability27.66 Å3ChemAxon
Number of Rings3ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
SpectraNot Available
Synthesis ReferenceNot Available
General Reference
  1. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL: PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 May 3;447(7140):87-91. Epub 2007 Apr 22. Pubmed
  2. Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S, Leonard EM, Almstead NG, Ju W, Peltz SW, Miller LL: Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol. 2007 Apr;47(4):430-44. Pubmed
  3. Hamed SA: Drug evaluation: PTC-124—a potential treatment of cystic fibrosis and Duchenne muscular dystrophy. IDrugs. 2006 Nov;9(11):783-9. Pubmed
External Links
PubChem Compound11219835
PubChem Substance29203630
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Drug InteractionsNot Available
Food InteractionsNot Available
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Drug created on October 21, 2007 16:23 / Updated on September 16, 2013 17:26