Ledipasvir (GS5885)

Alias: Ledipasvir; GS-5885, GS5885; GS 5885; trade name: Harvoni;
Cat No.:V0728 Purity: ≥98%
Ledipasvir (formerly GS5885; GS-5885; trade name Harvoni) is a novel and potent HCV NS5A polymerase inhibitor that is used for the treatment of HCV-hepatitis C virus infection.
Ledipasvir (GS5885) Chemical Structure CAS No.: 1256388-51-8
Product category: Reverse Transcriptase
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
Other Sizes

Other Forms of Ledipasvir (GS5885):

  • Ledipasvir acetone
  • Ledipasvir D-tartrate
  • Ledipasvir-d6 (GS-5885-d6)
  • Ledipasvir hydrochloride (GS-5885 hydrochloride)
  • Ledipasvir (diacetone)
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Ledipasvir (formerly GS5885; GS-5885; trade name Harvoni) is a novel and potent HCV NS5A polymerase inhibitor that is used for the treatment of HCV-hepatitis C virus infection. As an inhibitor of the hepatitis C virus NS5A, it has EC50s of 34 pM and 4 pM against genotype 1a and 1b replicon, respectively. The combination product of ledipasvir 90 mg/sofosbuvir 400 mg (trade name Harvoni) was approved by FDA in October 2014. The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin. Ledipasvir has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. It has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
Ledipasvir's protein-adjusted EC50 values are 210 pM for GT1a and 27 pM for GT1b, and its intrinsic EC50 of 39 is 310 fM for GT1a and 40 fM for GT1b. Its GT1a and 1b EC50 values are 31 and 4 pM, respectively. Ledipasvir exhibits high levels of protein binding in both human serum and the cell-culture medium used in the replicon assay, which contains 10% BSA[1]. Ledipasvir's EC50 value against the JFH/3a-NS5A replicon is 141 nM [2].
ln Vivo
Ledipasvir is unique due to its low clearance, good bioavailability, long half-lives in rats, dogs, and monkeys, as well as its low projected clearance in humans, in addition to its high replicon potency. Ledipasvir's pharmacokinetics are assessed in dogs and rats. Ledipasvir exhibits low systemic clearance (CL), moderate volumes of distribution (Vss) that are more than total body water volume, and good half-lives (dog 2.63 ± 0.18 hr, rat 1.83 ± 0.22 hr) in plasma[1].
Animal Protocol
Pharmacokinetic studies are performed in male na ve Sprague-Dawley(SD) rats, non-naive beagle dogs, and cynomolgus monkeys (three animals per dosing route). Intravenous (IV) administration is dosed via infusion over 30 min in a vehicle containing 5% ethanol, 20% PEG400, and 75% water (pH adjusted to 3.0 with HCl). Oral dosing is administered by gavage in a vehicle containing 5% ethanol, 45% PEG 400, and 50% of 50 mM citrate buffer, pH 3. Blood samples are collected over a 24 h period postdose into Vacutainer tubes containing EDTA-K2. Plasma was isolated, and the concentration of the test compound in plasma was determined with LC/MS/MS after protein precipitation with acetonitrile.
PK studies in Rats, Dogs and Monkeys; Ledipasvir is remarkable not only on the basis of its high replicon potency but also on the basis of its low clearance, good bioavailability, and long half-lives in rat, dog, and monkey and low predicted clearance in human. The pharmacokinetics of Ledipasvir is measured in rats and dogs. Ledipasvir shows good half-lives (rat 1.83 ± 0.22 hr, dog 2.63 ± 0.18 hr) in plasma, low systemic clearance (CL), and moderate volumes of distribution (Vss) that are greater than total body water volume
References
[1]. Link JO, et al. Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection. J Med Chem. 2014 Mar 13;57(5):2033-46
[2]. Hernandez D, et al. Natural prevalence of NS5A polymorphisms in subjects infected with hepatitis C virus genotype 3 and their effects on the antiviral activity of NS5A inhibitors. J Clin Virol. 2013 May;57(1):13-8.
[3]. Qi Sun, et al. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C49H54F2N8O6
Molecular Weight
889.0
CAS #
1256388-51-8
SMILES
O=C(OC)N[C@@H](C(C)C)C(N([C@H](C1=NC=C(C2=CC(C(F)(F)C3=C4C=CC(C5=CC=C6C(NC([C@@H] 7[C@@](C8)([H])CC[C@@]8([H])N7C([C@@H](NC(OC)=O)C(C)C)=O)=N6)=C5)=C3)=C4C=C2)N1)C9)CC%109CC%10)=O
Chemical Name
Methyl N-[(2S)-1-[(6S)-6-[5-[9,9-Difluoro-7-[2-[(1S,2S,4R)-3-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-3-azabicyclo[2.2.1]heptan-2-yl]-3H-benzimidazol-5-yl]fluoren-2-yl]-1H-imidazol-2-yl]-5-azaspiro[2.4]heptan-5-yl]-3-methyl-1-oxobutan-2-yl]carbamate
Synonyms
Ledipasvir; GS-5885, GS5885; GS 5885; trade name: Harvoni;
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 100 mg/mL (112.5 mM)
Water:<1 mg/mL
Ethanol:100 mg/mL (112.5 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.1249 mL 5.6243 mL 11.2486 mL
5 mM 0.2250 mL 1.1249 mL 2.2497 mL
10 mM 0.1125 mL 0.5624 mL 1.1249 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Biological Data
  • Ledipasvir (GS5885)
    J Med Chem.2014 Mar 13;57(5):2033-46.
  • Ledipasvir (GS5885)

    Nature. 2010 May 6;465(7294):96-100.
  • Ledipasvir (GS5885)

    Nature. 2010 May 6;465(7294):96-100.
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