| Size | Price | Stock | Qty |
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| 50mg |
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| 250mg |
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Purity: ≥98%
Laninamivir (Inavir, CS-8958, R-125489) is a novel and potent neuraminidase inhibitor with antiviral activities. It inhibits avian H12N5 NA (N5), pH1N1 N1 NA (p09N1) and A/RI/5+/1957 H2N2 N2 (p57N2) strains with IC50s of 0.90 nM, 1.83 nM and 3.12 nM, respectively. Laninamivir exhibits clinical efficacy for both treatment and prophylaxis of influenza virus infection, resulting from hydrolytic bioactivation into its pharmacologically active metabolite laninamivir in the pulmonary tissue.
| Targets |
N5(IC50= 0.90 nM);p09N1(IC50= 1.83 nM);p57N2(IC50= 3.12 nM)
Influenza virus neuraminidase (NA) [1] |
|---|---|
| ln Vitro |
Common oseltamivir-resistant viruses, including those with the common His274Tyr substitution, are effectively inhibited by laninamivir (R 125489)[1].
Like Zanamivir, laninamivir (R 125489) has a similar binding mechanism and is effective against p57N2, p09N1, and N5[1]. Laninamivir potently inhibited neuraminidase activity from various influenza A virus strains in vitro. The inhibitory potency (IC50) varied depending on the NA group and subtype. Against a typical group 1 NA (avian H12N5 N5), the IC50 was 0.90 nM. Against an atypical group 1 NA (2009 pandemic H1N1 p09N1), the IC50 was 1.83 nM. Against a typical group 2 NA (1957 pandemic H2N2 p57N2), the IC50 was 3.12 nM. Laninamivir inhibition was 1.53, 1.65, and 2.29-fold lower than zanamivir for N5, p09N1, and p57N2, respectively. The prodrug, laninamivir octanoate (CS-8958), showed weaker direct NA inhibition with IC50 values of 389 nM (N5), 947 nM (p09N1), and 129 nM (p57N2). [1] Structural analysis revealed that laninamivir binds to NA active sites with a mode highly similar to zanamivir and the transition state analogue Neu5Ac2en. Its 4-guanidino group is buried deep beneath the 150-loop, forming key hydrogen bonds. The presence of a pre-existing 150-cavity (as in group 1 N5) facilitated better inhibition compared to NAs lacking this cavity (p09N1, p57N2). [1] The binding mode of laninamivir octanoate to NA differed between subtypes. In p57N2, it bound similarly to laninamivir with an additional hydrogen bond between its 9-ester carbonyl and Arg224. In p09N1, it adopted a unique binding mode where Glu276 rotated to form a salt bridge with Arg224 (similar to oseltamivir binding), creating a hydrophobic pocket, and the 9-ester-O formed a hydrogen bond with Asn294. This binding in p09N1 was less stable compared to its binding in p57N2. [1] |
| Enzyme Assay |
A neuraminidase inhibition assay was performed using methylumbelliferyl-N-acetylneuraminic acid (MUNANA) as the substrate. Briefly, 10 µL of purified recombinant neuraminidase (10 nM) was mixed with 10 µL of serially diluted inhibitor and incubated for 30 minutes at room temperature. Following incubation, 30 µL of 166 µM MUNANA in 33 mM MES buffer (pH 6.0) containing 4 mM CaCl2 was added to start the reaction. The fluorescence generated by the enzymatic cleavage of MUNANA was quantified over 30 minutes using a plate reader (excitation 355 nm, emission 460 nm). A single time point was chosen where the positive control (no inhibitor) produced a fluorescence signal of approximately 1,000. All assays were performed in triplicate. IC50 values were calculated by fitting the log[inhibitor] versus inhibition percentage data using sigmoidal curve fitting in GraphPad Prism software. [1]
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| ADME/Pharmacokinetics |
The prodrug lanimivir caprylate (CS-8958) is processed in the lungs into the active form lanimivir (R-125489). This property, along with the 7-methoxy group on lanimivir, increases the drug's residence time in the lungs, thus enabling efficient single-dose inhalation administration. [1]
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| References | |
| Additional Infomation |
Laninamivir belongs to the acetamide class of compounds. Laninamivir has been used in clinical trials for the treatment of influenza. Laninamivir is a novel and potent influenza neuraminidase inhibitor. Its core structure is based on the neuraminidase transition state analog Neu5Ac2en (DANA). It contains a 4-guanidino group (similar to zanamivir) and an additional 7-methoxy group. [1] Laninamivir and its octanoate prodrug (CS-8958) have been approved for marketing in Japan (trade name Inavir). The prodrug is administered by a single inhalation. [1] In vitro studies have demonstrated that Laninamivir is effective against oseltamivir-resistant viruses, including those with common His274Tyr substitutions in N1 neuraminidase. [1]
This study suggests that inhibitors like lanimivir and zanamivir, which are structurally highly similar to the natural substrate transition state (Neu5Ac2en), are more likely to remain effective against neuraminidase (NA) from different phylogenetic groups and with resistance mutations. [1] The text cites a clinical study (not conducted in this paper) that showed that in adult patients, lanimivir caprylate was not significantly more effective than oseltamivir against oseltamivir-resistant His274Tyr H1N1 infection. The authors speculate that this may be because the prodrug binds to atypical group 1 NA (p09N1) in a similar manner to oseltamivir, or because it is converted to active lanimivir more slowly in adults. [1] |
| Molecular Formula |
C13H22N4O6
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|---|---|
| Molecular Weight |
346.33638
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| Exact Mass |
346.148
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| Elemental Analysis |
C, 45.08; H, 6.40; N, 16.18; O, 32.34
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| CAS # |
203120-17-6
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| Related CAS # |
Laninamivir octanoate;203120-46-1;Laninamivir octanoate hydrate;1233643-88-3
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| PubChem CID |
502272
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| Appearance |
White to off-white solid powder
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| Density |
1.6±0.1 g/cm3
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| Index of Refraction |
1.634
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| LogP |
-3.06
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
24
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| Complexity |
532
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CC(N[C@@H]1[C@@H](NC(N)=N)C=C(O[C@H]1[C@H](OC)[C@H](O)CO)C(O)=O)=O
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| InChi Key |
LANWZBLPTYVJPY-PKIKSRDPSA-N
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| InChi Code |
InChI=1S/C13H22N4O6/c1-6(19)16-11-8(17-13(14)15)4-10(12(20)21)23-9(11)3-7(5-18)22-2/h4,7-9,11,18H,3,5H2,1-2H3,(H,16,19)(H,20,21)(H4,14,15,17)/t7-,8+,9-,11-/m1/s1
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| Chemical Name |
(2R,3R,4S)-3-acetamido-4-guanidino-2-((R)-3-hydroxy-2-methoxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid
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| Synonyms |
CS8958; CS-8958; CS 8958;R-125489; R 125489; R125489;
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| HS Tariff Code |
2934.99.03.00
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| 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)
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| Solubility (In Vitro) |
H2O : ~5 mg/mL (~14.44 mM )
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3.12 mg/mL (9.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8873 mL | 14.4367 mL | 28.8734 mL | |
| 5 mM | 0.5775 mL | 2.8873 mL | 5.7747 mL | |
| 10 mM | 0.2887 mL | 1.4437 mL | 2.8873 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02022761 | COMPLETED | Drug: Laninamivir octanoate | Asthma | Biota Scientific Management Pty Ltd | 2013-10 | Phase 1 |
| NCT01793883 | COMPLETEDWITH RESULTS | Drug: 40 mg Laninamivir Octanoate Drug: 80 mg Laninamivir Octanoate Drug: Placebo |
Influenza | Biota Scientific Management Pty Ltd | 2013-05 | Phase 2 |
| NCT02014649 | TERMINATED | Drug: 20 mg laninamivir octanoate Drug: Placebo Drug: 40 mg laninamivir octanoate |
Influenza | Biota Scientific Management Pty Ltd | 2013-11 | Phase 1 Phase 2 |
| NCT00995826 | COMPLETED | Drug: CS-8958 Other: Placebo |
Influenza | Biota Scientific Management Pty Ltd | 2009-04 | Phase 1 |
| NCT05648448 | RECRUITING | Drug: Oseltamivir |
Influenza Influenza, Human |
University of Oxford | 2023-02-22 | Phase 2 |
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