775304-57-9

775304-57-9 structure

Name: Ataluren (PTC124)
Chemical Name: 3-(5-(2-Fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoic acid
CAS Number: 775304-57-9
Molecular Formula: C₁₅H₉FN₂O₃
Molecular Weight: 284.242
Catalog: Biochemical Inhibitor Transmembrane Transporters CFTR inhibitor
Create Date: 2018-08-02 10:23:52
Modify Date: 2024-01-02 15:32:45
Ataluren (PTC124) is an orally available CFTR-G542X nonsense allele inhibitor.

Name	3-(5-(2-Fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoic acid
Synonyms	3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid Ataluren Benzoic acid, 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]- PTC124

Description	Ataluren (PTC124) is an orally available CFTR-G542X nonsense allele inhibitor.
Related Catalog	Signaling Pathways >> Membrane Transporter/Ion Channel >> CFTR Research Areas >> Metabolic Disease
Target	CFTR[1]
In Vitro	This premature “stop” signal (a class I mutation) prevents the cell from producing a full-length CFTR protein[1]. Ataluren (PTC124)-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons[2].
In Vivo	Ataluren (PTC124) activity, optimized using nonsense-containing reporters, promotes dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescues striated muscle function in mdx mice within 2-8 weeks of drug exposure. Ataluren (PTC124) is well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression[2]. To induce nonsense suppression and increase PPT1 enzyme activity, the read-through drug Ataluren (PTC124) is given via intraperitoneal (i.p.) injection to male Cln1R151X mice at 2 months of age. These treatments are performed four times daily for 2 consecutive days in a proof-of-principle study. Used at 10 mg/kg, Ataluren (PTC124) increased PPT1 enzyme activity (P=0.0001 by unpaired t-test) and protein level (P=0.0014 by unpaired t-test) in the liver, but did not increase PPT1 enzyme activity or protein level in the cortex. This tissue-specific effect is likely due to the inability of Ataluren (PTC124) to breach the blood brain barrier (BBB), which decreased the bioavailability of Ataluren (PTC124) within the brain, and prevented Ataluren (PTC124) from reaching an efficacious concentration within the therapeutic window[3].
Cell Assay	Duplicate samples of HEK293 cells harbouring LUC-190 (UGA) are incubated in the presence of 5 μM Ataluren (PTC124) (treated) or 1% DMSO (untreated) for 20 h. The cells are collected, washed twice in phosphate buffered saline (PBS), resuspended in sample buffer (Bio-Rad) and shipped on dry ice to Kendrick Laboratories for two-dimensional electrophoretic analysis Isoelectric focusing (pH 3.5-10) is carried out in glass tubes for 20,000 V-hours. One μg of a tropomyosin internal standard is added to each sample. Second dimension SDS slab gel electrophoresis is carried out for approximately 6 h at 25 mA per gel. After electrophoresis, gels are transferred to PVDF paper. Computerized analysis of spot mobility used Phoretix software[2].
Animal Admin	Mice[3] Male mice are randomly assigned to either a treatment group or vehicle control group. Six to eight mice per group are treated with 10 or 100 mg/kg Ataluren (PTC124) dissolved in PBS containing DMSO (2% for 10 mg/kg and 20% for 100 mg/kg) and (2-hydroxypropyl)-β-cyclodextrin (22%) via intraperitoneal (i.p.) injections four times daily for 2 consecutive days. Six to eight control mice are treated with the vehicle of the drug: PBS containing DMSO (2% or 20%) and (2-hydroxypropyl)-β-cyclodextrin (22%). Immediately following the last injection on the second day, tissues are collected and stored at −80°C for further use.
References	[1]. Pettit RS, et al. CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014 Jul;39(7):500-11. [2]. Welch EM, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature, 2007, 447(7140), 87-91. [3]. Miller JN, et al. The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy. Hum Mol Genet. 2015 Jan 1;24(1):185-96.

Density	1.4±0.1 g/cm3
Boiling Point	503.7±60.0 °C at 760 mmHg
Molecular Formula	C₁₅H₉FN₂O₃
Molecular Weight	284.242
Flash Point	258.4±32.9 °C
Exact Mass	284.059723
PSA	76.22000
LogP	3.73
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.604

Material Safety Data Sheet

Section1. Identiﬁcation of the substance
Product Name: Ataluren
Synonyms:

Section2. Hazards identiﬁcation
Harmful by inhalation, in contact with skin, and if swallowed.

Section3. Composition/information on ingredients.
Ingredient name:Ataluren
CAS number:775304-57-9

Section4. First aid measures
Skin contact:Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact:Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
ﬂushing of the eyes by separating the eyelids with ﬁngers. If irritation persists, seek medical
attention.
Inhalation:Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion:Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

Section5. Fire ﬁghting measures
In the event of a ﬁre involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

Section6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution:Wear approved mask/respirator
Hand precaution:Wear suitable gloves/gauntlets
Skin protection:Wear suitable protective clothing
Eye protection:Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

Section7. Handling and storage
Handling:This product should be handled only by, or under the close supervision of, those properly qualiﬁed
in the handling and use of potentially hazardous chemicals, who should take into account the ﬁre,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

Section8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

Section9. Physical and chemical properties
Appearance:Not speciﬁed
Boiling point:No data
No data
Melting point:
Flash point:No data
Density:No data
Molecular formula:C15H9FN2O3
Molecular weight:284.2

Section10. Stability and reactivity
Conditions to avoid: Heat, ﬂames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen ﬂuoride.

Section11. Toxicological information
No data.

Section12. Ecological information
No data.

Section13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

Section14. Transportation information
Non-harzardous for air and ground transportation.

Section15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

SECTION 16 - ADDITIONAL INFORMATION
N/A

Hazard Codes	Xi
HS Code	2934999090

775304-60-4

~95%

775304-57-9

Literature: PTC THERAPEUTICS, INC. Patent: WO2007/117438 A2, 2007 ; Location in patent: Page/Page column 261 ;

393-52-2

~78%

775304-57-9

Literature: PTC THERAPEUTICS, INC. Patent: WO2008/30570 A1, 2008 ; Location in patent: Page/Page column 23-24 ;

1141475-82-2

393-52-2

775304-57-9

Literature: Bioorganic and Medicinal Chemistry Letters, , vol. 24, # 11 p. 2473 - 2476

Precursor 3
775304-60-4 393-52-2 1141475-82-2
DownStream 0

HS Code	2934999090
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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