Preferred Label : Givosiran Sodium;
NCIt synonyms : ALN AS1 Sodium;
NCIt definition : The sodium salt form of givosiran, an enhanced stabilization chemistry (ESC)-stabilized
conjugate composed of the liver-targeted ligand N-acetylgalactosamine (GalNAc) conjugated
to small-interfering RNAs (siRNAs) directed against the liver-expressed enzyme aminolevulinic
acid synthase 1 (delta-aminolevulinate synthase 1; ALAS1; ALAS-1) that can potentially
be used in the treatment of acute hepatic porphyrias (AHPs). Upon subcutaneous administration
of givosiran, the GalNAc moiety targets and binds with high affinity to asialoglycoprotein
receptors (ASGPRs) expressed on hepatocytes. Once inside the cell, the siRNAs bind
to and silence ALAS1 mRNA and inhibit both the translation and expression of the ALAS1
protein. This prevents delta-aminolevulinic acid (ALA) formation, decreases 5-ALA
levels and prevents the production of porphyrins and hemes, such as porphobilinogen
(PBG). AHPs are a group of metabolic disorders caused by deficiencies of specific
enzymes that are responsible for hemoglobulin biosynthesis within the liver, which
leads to the accumulation of toxic intermediates, such as ALA and PBG. ALAS1, a liver-expressed,
rate-limiting enzyme in the heme biosynthesis pathway, is responsible for the formation
of ALA from succinyl-CoA and glycine. ESC enables the subcutaneous dosing of givosiran
with increased efficacy, durability and a wide therapeutic index as compared to non-ESC
GalNAc-siRNA conjugates.;
UNII : 5XE21E41RT;
Drug name : Givlaari;
NCI Metathesaurus CUI : CL1412862;
Origin ID : C175519;
UMLS CUI : C5221241;
Currated CISMeF NLP mapping
- Semantic type(s)
- UMLS correspondences (same concept)
- concept_is_in_subset
- has_free_acid_or_base_form
- is_salt_form_of
