"目录号: HY-14832
Membrane Transporter/Ion Channel-
PTC124靶向作用于无义突变，将终止密码子插入到CFTR基因中间。
相关产品
VX-809-Ivacaftor-CFTR(inh)-172-GlyH-101-VX-661-BPO-27 racemate-IOWH-032-PPQ-102-KM11060-
生物活性
Description
PTC124 targets nonsense mutations, which insert a termination codon in the middle of theCFTRgene.
IC50& Target
CFTR[1]
In Vitro
This premature “stop” signal (a class I mutation) prevents the cell from producing a full-length CFTR protein[1]. PTC124 (Ataluren)-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons[2].
In Vivo
PTC124 (Ataluren) activity, optimized using nonsense-containing reporters, promotes dystrophin production in primary muscle cells from humans andmdxmice expressing dystrophin nonsense alleles, and rescues striated muscle function inmdxmice within 2-8?weeks of drug exposure. 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 PTC124 (Ataluren) is given via intraperitoneal (i.p.) injection to maleCln1R151Xmice 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, 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 PTC124 to breach the blood brain barrier (BBB), which decreased the bioavailability of PTC124 within the brain, and prevented PTC124 from reaching an efficacious concentration within the therapeutic window[3].
Clinical Trial
PTC Therapeutics
Cystic Fibrosis
July 2015
Phase 3
PTC Therapeutics
Duchenne Muscular Dystrophy
June 2016
Phase 2
PTC Therapeutics
Muscular Dystrophy, Duchenne-Muscular Dystrophies-Muscular Disorders, Atrophic-Muscular Diseases-Musculoskeletal Diseases-Neuromuscular Diseases-Nervous System Diseases-Genetic Diseases, X-Linked-Genetic Diseases, Inborn
March 2014
Phase 3
New York University School of Medicine-PTC Therapeutics
Epilepsy
November 2016
Phase 2
PTC Therapeutics
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy-Dystrophinopathy
May 2012
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy
November 2009
Phase 2
PTC Therapeutics-Cystic Fibrosis Foundation Therapeutics
Cystic Fibrosis
August 2010
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Duchenne Muscular Dystrophy
July 2008
Phase 2
PTC Therapeutics-Genzyme, a Sanofi Company
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy
January 2009
Phase 2-Phase 3
PTC Therapeutics
Muscular Dystrophy, Duchenne-Muscular Dystrophies-Muscular Disorders, Atrophic-Muscular Diseases-Musculoskeletal Diseases-Neuromuscular Diseases-Nervous System Diseases-Genetic Diseases, X-Linked-Genetic Diseases, Inborn
March 2013
Phase 3
PTC Therapeutics-Cystic Fibrosis Foundation Therapeutics
Cystic Fibrosis
July 2009
Phase 3
PTC Therapeutics
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy
November 2010
Phase 3
PTC Therapeutics
Aniridia
January 2016
Phase 2
PTC Therapeutics
Cystic Fibrosis
May 2014
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Amino Acid Metabolism, Inborn Errors
June 2010
Phase 2
PTC Therapeutics
Muscular Dystrophy, Duchenne-Muscular Dystrophies-Muscular Disorders, Atrophic-Muscular Diseases-Musculoskeletal Disease-Neuromuscular Diseases-Nervous System Diseases-Genetic Diseases, X-Linked-Genetic Diseases, Inborn
July 6, 2017
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Hemophilia A-Hemophilia B
August 2009
Phase 2
PTC Therapeutics
Healthy
March 2015
Phase 1
PTC Therapeutics-Cystic Fibrosis Foundation Therapeutics-European Cystic Fibrosis Society-Clinical Trial Network (ECFS-CTN)
Cystic Fibrosis
June 2014
Phase 3
PTC Therapeutics
Cystic Fibrosis
July 2015
Phase 3
PTC Therapeutics
Duchenne Muscular Dystrophy
June 2016
Phase 2
PTC Therapeutics
Muscular Dystrophy, Duchenne-Muscular Dystrophies-Muscular Disorders, Atrophic-Muscular Diseases-Musculoskeletal Diseases-Neuromuscular Diseases-Nervous System Diseases-Genetic Diseases, X-Linked-Genetic Diseases, Inborn
March 2014
Phase 3
New York University School of Medicine-PTC Therapeutics
Epilepsy
November 2016
Phase 2
PTC Therapeutics
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy-Dystrophinopathy
May 2012
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy
November 2009
Phase 2
PTC Therapeutics-Cystic Fibrosis Foundation Therapeutics
Cystic Fibrosis
August 2010
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Duchenne Muscular Dystrophy
July 2008
Phase 2
PTC Therapeutics-Genzyme, a Sanofi Company
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy
January 2009
Phase 2-Phase 3
PTC Therapeutics
Muscular Dystrophy, Duchenne-Muscular Dystrophies-Muscular Disorders, Atrophic-Muscular Diseases-Musculoskeletal Diseases-Neuromuscular Diseases-Nervous System Diseases-Genetic Diseases, X-Linked-Genetic Diseases, Inborn
March 2013
Phase 3
PTC Therapeutics-Cystic Fibrosis Foundation Therapeutics
Cystic Fibrosis
July 2009
Phase 3
PTC Therapeutics
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy
November 2010
Phase 3
PTC Therapeutics
Aniridia
January 2016
Phase 2
PTC Therapeutics
Cystic Fibrosis
May 2014
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Amino Acid Metabolism, Inborn Errors
June 2010
Phase 2
PTC Therapeutics
Muscular Dystrophy, Duchenne-Muscular Dystrophies-Muscular Disorders, Atrophic-Muscular Diseases-Musculoskeletal Disease-Neuromuscular Diseases-Nervous System Diseases-Genetic Diseases, X-Linked-Genetic Diseases, Inborn
July 6, 2017
Phase 3
PTC Therapeutics-Genzyme, a Sanofi Company
Hemophilia A-Hemophilia B
August 2009
Phase 2
PTC Therapeutics
Healthy
March 2015
Phase 1
PTC Therapeutics-Cystic Fibrosis Foundation Therapeutics-European Cystic Fibrosis Society-Clinical Trial Network (ECFS-CTN)
Cystic Fibrosis
June 2014
Phase 3
PTC Therapeutics
Duchenne Muscular Dystrophy-Becker Muscular Dystrophy
February 2008
Phase 2-Phase 3
PTC Therapeutics-Muscular Dystrophy Association
Duchenne Muscular Dystrophy
December 2005
Phase 2
PTC Therapeutics
Cystic Fibrosis
December 2006
Phase 2
PTC Therapeutics-Cystic Fibrosis Foundation Therapeutics-FDA Office of Orphan Products Development
Cystic Fibrosis
September 2005
Phase 2
PTC Therapeutics
Cystic Fibrosis
March 2007
Phase 2
PTC Therapeutics
Cystic Fibrosis
November 2005
Phase 2
View MoreCollapse
References
[1].Pettit RS, et al. CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014 Jul;39(7):500-11.
