Cipaglucosidase alfa; Recombinant Human acid alpha-glucosidase

Specification

• Cat#: THP-1102
• Product Name: Cipaglucosidase alfa; Recombinant Human acid alpha-glucosidase
• Description: Cipaglucosidase alfa is a recombinant human acid alpha-glucosidase used to treat late-onset Pompe disease in adults.
• Sequences: QQGASRPGPRDAQAHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQGLQGAQMGQPWCFFPPSYPSYKLENLSSSEMGYTATLTRTTPTFFPKDILTLRLDVMMETENRLHFTIKDPANRRYEVPLETPHVHSRAPSPLYSVEFSEEPFGVIVRRQLDGRVLLNTTVAPLFFADQFLQLSTSLPSQYITGLAEHLSPLMLSTSWTRITLWNRDLAPTPGANLYGSHPFYLALEDGGSAHGVFLLNSNAMDVVLQPSPALSWRSTGGILDVYIFLGPEPKSVVQQYLDVVGYPFMPPYWGLGFHLCRWGYSSTAITRQVVENMTRAHFPLDVQWNDLDYMDSRRDFTFNKDGFRDFPAMVQELHQGGRRYMMIVDPAISSSGPAGSYRPYDEGLRRGVFITNETGQPLIGKVWPGSTAFPDFTNPTALAWWEDMVAEFHDQVPFDGMWIDMNEPSNFIRGSEDGCPNNELENPPYVPGVVGGTLQAATICASSHQFLSTHYNLHNLYGLTEAIASHRALVKARGTRPFVISRSTFAGHGRYAGHWTGDVWSSWEQLASSVPEILQFNLLGVPLVGADVCGFLGNTSEELCVRWTQLGAFYPFMRNHNSLLSLPQEPYSFSEPAQQAMRKALTLRYALLPHLYTLFHQAHVAGETVARPLFLEFPKDSSTWTVDHQLLWGEALLITPVLQAGKAEVTGYFPLGTWYDLQTVPVEALGSLPPPPAAPREPAIHSEGQWVTLPAPLDTINVHLRAGYIIPLQGPGLTTTESRQQPMALAVALTKGGEARGELFWDDGESLEVLERGAYTQVIFLARNNTIVNELVRVTSEGAGLQLQKVTVLGVATAPQQVLSNGVPVSNFTYSPDTKVLDICVSLLMGEQFLVSWC
• Species: Human
• Molecular Weight: 99400.0 Da (approximate)
• Introduction: Cipaglucosidase alfa is a novel recombinant human acid alpha-glucosidase (GAA) investigated for the treatment of patients with Pompe disease, a rare inherited metabolic disorder characterized by a deficiency in GAA. Other types of enzyme replacement therapy for the treatment of Pompe disease include alglucosidase alfa and avalglucosidase alfa. Cipaglucosidase alfa is conjugated with mannose-6-phosphate (M6P) N-glycans that bind to the cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, one of the main affected tissues in Pompe disease. Compared to alglucosidase alfa, cipaglucosidase alfa has a higher M6P content. In December 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended cipaglucosidase alfa be granted marketing authorization for the treatment of Pompe disease, and the EMA fully approved the drug on March 27, 2023. Cipaglucosidase alfa is coadministered with miglustat, a small-molecule pharmacological chaperone that stabilizes the conformation of the enzyme. In September 2023, the FDA also approved cipaglucosidase alfa for similar indications.
• Cas No: 2359727-71-0
• Formula: C4489H6796N1197O1298S32
• Biologic Classification: Protein Based Therapies Recombinant Enzymes
• Physical Appearance: Liquid

Pharmaceutical Information

• Pharmacodynamics: Cipaglucosidase alfa is a long-term enzyme replacement therapy that aims to break down glycogen and attenuate tissue damage in late-onset Pompe disease. Clinical studies demonstrate improved walking distance and stabilization of pulmonary function following the treatment with cipaglucosidase alfa. While cipaglucosidase alfa is reported to exhibit better cellular uptake and lysosomal trafficking compared to other existing replacement therapies, one study reported that cipaglucosidase alfa plus miglustat did not achieve statistical superiority to alglucosidase alfa plus placebo for improving 6-min walk distance in patients with late-onset Pompe disease.
• Mechanism of action: Pompe disease, also known as glycogen storage disease type II (GSD II), is a rare inherited disorder caused by alpha-glucosidase (GAA) gene mutations. In normal conditions, GAA hydrolyzes glycogen and releases free glucose units in lysosomes. However, patients with Pompe disease have a GAA deficiency, and glycogen accumulates within lysosomes, impairing the function of smooth, cardiac, and skeletal muscle cells and causing tissue damage. Cipaglucosidase alfa is a recombinant form of GAA conjugated with mannose-6-phosphate (M6P) N-glycans. Attributing to M6P, cipaglucosidase alfa has a high affinity for the cation-independent mannose-6-phosphate receptor (CI-MPR), a receptor responsible for the transport of GAA to lysosomes. Upon binding to CI-MPR, cipaglucosidase alfa is internalized by the lysosomes and undergoes proteolytic cleavage and N-glycan trimming to form the mature and active form of the GAA enzyme to cleave glycogen. Cipaglucosidase alfa is coadministered with miglustat, which stabilizes the conformation of the enzyme.
• Targets: 1. Cation-independent mannose-6-phosphate receptor; 2. Alpha glucosidase (GAA)