Size | Price | Stock | Qty |
---|---|---|---|
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
Other Sizes |
|
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. 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.
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 |
|
||
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 |
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 (In Vitro) |
|
---|
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.
Calculation results
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.
(2) Be sure to add the solvent(s) in order.