Givosiran API (CAS No. 1639325-43-1) is a chemically modified, double-stranded small interfering RNA active pharmaceutical ingredient associated with RNA interference therapeutics, acute hepatic porphyria, liver-targeted oligonucleotide medicines, and rare disease pharmaceutical development.
Givosiran belongs to the small interfering RNA, commonly abbreviated as siRNA, class of therapeutic oligonucleotides.
Unlike conventional synthetic small-molecule APIs, Givosiran is a complex chemically modified oligonucleotide therapeutic designed to regulate disease-associated gene expression through RNA interference.
Givosiran is directed against aminolevulinate synthase 1, commonly abbreviated as ALAS1.
ALAS1 is the first and rate-limiting enzyme involved in hepatic heme biosynthesis.
Givosiran causes degradation of ALAS1 messenger RNA in hepatocytes through the RNA interference pathway.
Reduction of hepatic ALAS1 mRNA decreases production of ALAS1 protein and reduces elevated levels of neurotoxic heme pathway intermediates, including aminolevulinic acid and porphobilinogen.
These intermediates are commonly abbreviated as ALA and PBG and are associated with acute attacks and other clinical manifestations of acute hepatic porphyria.
Givosiran is covalently linked to a ligand containing three N-acetylgalactosamine residues.
The triantennary N-acetylgalactosamine ligand, commonly referred to as GalNAc, enables targeted delivery of the siRNA therapeutic to hepatocytes.
GalNAc-mediated liver targeting is an important pharmaceutical characteristic of Givosiran because ALAS1 gene silencing is intended to occur primarily within hepatocytes.
Givosiran is associated with subcutaneous injectable pharmaceutical products for the treatment of acute hepatic porphyria in adults.
Pharmaceutical companies and oligonucleotide development organizations evaluating Givosiran API commonly focus on oligonucleotide sequence identity, strand identity, RNA duplex integrity, conjugate identity, GalNAc ligand integrity, oligonucleotide purity, related oligonucleotide impurities, truncated sequences, elongated sequences, depurination products, deamination products, oxidation products, residual solvents, elemental impurities, bioburden, bacterial endotoxins, and batch-to-batch consistency.
Because Givosiran is a chemically modified siRNA conjugate, conventional small-molecule API specifications such as melting point, simple HPLC assay, and conventional specific rotation may not be appropriate as primary quality attributes.
Givosiran and Givosiran Sodium should be treated as separate material identities for procurement, analytical, formulation, and pharmaceutical development purposes.
Swapnroop Drugs and Pharmaceuticals supports Givosiran API sourcing and supply coordination for qualified pharmaceutical research, RNA interference drug development, oligonucleotide analytical development, rare disease pharmaceutical research, and advanced pharmaceutical development requirements with product-specific documentation and specialized material-handling coordination.
Givosiran is a double-stranded small interfering RNA therapeutic.
The siRNA is designed to target messenger RNA encoding aminolevulinate synthase 1.
Following hepatocyte delivery, Givosiran participates in the cellular RNA interference pathway.
The antisense strand directs the RNA interference machinery toward complementary ALAS1 messenger RNA.
Targeted ALAS1 mRNA is degraded.
Reduction of ALAS1 messenger RNA decreases elevated hepatic ALAS1 expression.
Reduced ALAS1 activity leads to decreased production of aminolevulinic acid and porphobilinogen.
ALA and PBG are neurotoxic intermediates associated with acute hepatic porphyria attacks and other disease manifestations.
The RNA interference mechanism enables sequence-directed reduction of a disease-associated hepatic target.
ALAS1 is the first and rate-limiting enzyme in the hepatic heme biosynthesis pathway.
In acute hepatic porphyria, defects involving downstream enzymes in the heme biosynthesis pathway can contribute to induction of hepatic ALAS1.
Elevated ALAS1 activity contributes to increased production of heme pathway intermediates.
Givosiran is designed to reduce elevated ALAS1 mRNA levels in hepatocytes.
Reduction of ALAS1 expression decreases production of ALA and PBG.
The ALAS1-directed mechanism is a central pharmaceutical characteristic of Givosiran.
Givosiran is covalently linked to a ligand containing three N-acetylgalactosamine residues.
This triantennary GalNAc ligand enables delivery of the siRNA to hepatocytes.
GalNAc conjugation is widely associated with liver-targeted oligonucleotide pharmaceutical development.
Important GalNAc conjugate quality considerations may include:
GalNAc ligand integrity should be evaluated according to the approved product-specific analytical strategy.
Givosiran and Givosiran Sodium should be distinguished during pharmaceutical material sourcing.
Givosiran free acid has the molecular formula C524H694F16N173O316P43S6.
The molecular weight of Givosiran free acid is approximately 16,300.34 Da.
Givosiran Sodium has the molecular formula C524H651F16N173Na43O316P43S6.
The molecular weight of Givosiran Sodium is approximately 17,245.56 Da.
The pharmaceutical drug substance used in the commercial injectable product is structurally described in its sodium form.
Procurement, analytical, formulation, quality, and regulatory teams should confirm the exact Givosiran material form and counterion specification before commercial sourcing.
Givosiran-related pharmaceutical products are associated with subcutaneous injection.
Injectable development considerations may include:
The exact drug-substance and drug-product specifications should be separately established according to the intended pharmaceutical development program.
Analytical characterization of Givosiran API may include:
Because Givosiran is a complex siRNA conjugate, analytical control strategies should be designed specifically for oligonucleotide and conjugated RNA therapeutic materials.
Swapnroop Drugs and Pharmaceuticals supports qualified pharmaceutical and advanced therapeutic development customers with:
Givosiran API requires specialized pharmaceutical packaging appropriate for complex oligonucleotide and RNA-conjugate materials.
Packaging should be selected according to the exact supplied material form, concentration, counterion form, stability profile, moisture sensitivity, temperature requirements, and approved product specification.
Available supply configurations may include:
Packaging may include product-appropriate pharmaceutical-grade primary containers with suitable protection against contamination and environmental exposure.
Exact packaging configuration, MOQ, quantity, storage requirements, temperature conditions, and shipment conditions should be confirmed according to the approved material specification and customer enquiry.
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