| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
SYK (IC50 = 9.5 nM)
SYK (Spleen Tyrosine Kinase). |
|---|---|
| ln Vitro |
Lanraplenib succinate (GS-9876 succinate) inhibits the phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells stimulated by anti-IgM with EC50 values ranging from 24-51 nM. he anti-IgM mediated expression of CD69 and CD86 on B-cells (EC50=112±10 nM and 164±15 nM, respectively) as well as the co-stimulated B cell proliferation (EC50=108±55 nM) are inhibited by lanraplenib monosuccinate. Lanraplenib succinate (EC50=121±77 nM and 9±17 nM, respectively) inhibits the release of TNFα and IL-1β when IC is stimulated in human macrophages[1].
Lanraplenib succinate (GS-9876 succinate) prevents platelet activation and aggregation in human whole blood, platelet binding to collagen under arterial flow, and phosphorylation of the linker for T cell activation and phospholipase Cγ2 caused by glycoprotein VI (GPVI)[2]. Lanraplenib succinate (GS-9876 succinate) inhibits SYK activity with an IC50 of 9.5 nM. In human B cells, it inhibits anti-IgM-stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCdelta, with EC50 values reported. It is highly selective for SYK over other kinases, minimizing off-target effects. |
| ln Vivo |
In a phase 2 clinical trial (NCT03988400) in lupus, Lanraplenib demonstrated a favorable safety profile but did not achieve its primary endpoint of a reduction in the number of active joints in a large placebo-controlled study. However, the compound showed significant efficacy in multiple preclinical models of autoimmune disease and cancer.
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| Enzyme Assay |
Assay: In vitro SYK kinase inhibition assay. Protocol: Recombinant SYK protein is incubated with varying concentrations of Lanraplenib (e.g., 0.1-1000 nM), ATP, and a specific substrate peptide (e.g., biotinylated peptide derived from ITAM) in kinase reaction buffer. Phosphorylation is measured using a homogeneous time-resolved fluorescence (HTRF) or luminescent ADP-Glo assay. IC50 is calculated from dose-response curves.
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| Cell Assay |
Cells: Human B cells and platelets. Protocol: For B cell signaling, human PBMCs or isolated B cells are pre-incubated with Lanraplenib (0.1-1000 nM) for 1 hour, then stimulated with anti-IgM. Cells are lysed, and phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCdelta is analyzed by Western blot or ELISA. For platelet function, PRP is incubated with Lanraplenib (0.1-1000 nM), then aggregation is induced with collagen or other agonists.
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| Animal Protocol |
Animal Model: Cynomolgus monkeys and human bleeding time studies. Protocol: In monkeys, Lanraplenib is administered orally at doses of 3-30 mg/kg. Blood samples are collected to measure SYK inhibition in platelets. Bleeding time is measured via standard template bleeding time test from forearm incisions. Phase 1 clinical trials in healthy volunteers evaluated safety and PK. Efficacy was evaluated in Phase 2 trials in RA and lupus patients.
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| ADME/Pharmacokinetics |
Lanraplenib is orally bioavailable with good exposure. In clinical studies, it achieves plasma concentrations sufficient for target engagement and demonstrates dose-proportional PK. The compound is metabolized primarily in the liver and excreted via bile and urine. Its key feature is the ability to inhibit platelet SYK without prolonging bleeding time, indicating a favorable safety margin for thrombosis compared to bleeding.
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| Toxicity/Toxicokinetics |
Lanraplenib has demonstrated significant efficacy in multiple preclinical models of autoimmune disease and cancer, including collagen-induced arthritis (CIA) and lupus-prone mouse models. In healthy volunteers and RA patients, Lanraplenib (20-100 mg once daily) was generally well-tolerated with low rates of adverse events. It did not cause bleeding time prolongation. However, in a phase 2 lupus trial, Lanraplenib missed its primary endpoint.
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| References |
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| Additional Infomation |
Lanraplenib succinate is the succinate form of Lanraplenib, an orally administered spleen tyrosine kinase (Syk) inhibitor with potential immunomodulatory and antitumor activity. After oral administration, Lanraplenib binds to Syk and inhibits its activity. This inhibits B-cell receptor (BCR) signaling, thereby suppressing B-cell activation and preventing the activation, migration, adhesion, and proliferation of tumor cells. Syk is a non-receptor cytoplasmic tyrosine kinase associated with BCR, expressed in hematopoietic tissues, and often overexpressed in hematopoietic malignancies; it plays a crucial role in B-cell receptor signaling.
Lanraplenib (GS-9876) is a second-generation SYK inhibitor developed to improve upon the bleeding risk associated with first-generation SYK inhibitors (e.g., fostamatinib). Its inhibition of platelet SYK via the GPVI receptor is potent but reversible, which is thought to contribute to the lack of bleeding time prolongation. The compound is not FDA-approved but has been evaluated in clinical trials. |
| Molecular Formula |
C58H68N18O14
|
|---|---|
| Molecular Weight |
1241.27273082733
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| Exact Mass |
1240.52
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| Elemental Analysis |
C, 56.12; H, 5.52; N, 20.31; O, 18.04
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| CAS # |
1800047-00-0
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| Related CAS # |
Lanraplenib;1800046-95-0;Lanraplenib monosuccinate;1800046-97-2
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| PubChem CID |
133082362
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
10
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| Hydrogen Bond Acceptor Count |
30
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
90
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| Complexity |
728
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
SUXNLHAGYIRFJQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/2C23H25N9O.3C4H6O4/c2*24-21-12-25-11-19(28-21)20-13-32-6-5-26-23(32)22(29-20)27-16-1-3-17(4-2-16)30-7-9-31(10-8-30)18-14-33-15-18;3*5-3(6)1-2-4(7)8/h2*1-6,11-13,18H,7-10,14-15H2,(H2,24,28)(H,27,29);3*1-2H2,(H,5,6)(H,7,8)
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| Chemical Name |
6-(6-aminopyrazin-2-yl)-N-[4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl]imidazo[1,2-a]pyrazin-8-amine;butanedioic acid
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| Synonyms |
GS-SYK; GS-9876; GS 9876; GS9876
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO: ~83.3 mg/mL (~134.3 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8056 mL | 4.0281 mL | 8.0563 mL | |
| 5 mM | 0.1611 mL | 0.8056 mL | 1.6113 mL | |
| 10 mM | 0.0806 mL | 0.4028 mL | 0.8056 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.
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